Activation of PAR-1 Kinase and Stimulation of Tau Phosphorylation by Diverse Signals Require the Tumor Suppressor Protein LKB1
Open accessAbstract
Aberrant phosphorylation of tau is associated with a number of neurodegenerative diseases, including Alzheimer's disease (AD). The molecular mechanisms by which tau phosphorylation is regulated under normal and disease conditions are not well understood. Microtubule affinity regulating kinase (MARK) and PAR-1 have been identified as physiological tau kinases, and aberrant phosphorylation of MARK/PAR-1 target sites in tau has been observed in AD patients and animal models. Here we show that phosphorylation of PAR-1 by the tumor suppressor protein LKB1 is required for PAR-1 activation, which in turn promotes tau phosphorylation in Drosophila. Diverse stress stimuli, such as high osmolarity and overexpression of the human beta-amyloid precursor protein, can promote PAR-1 activation and tau phosphorylation in an LKB1-dependent manner. These results reveal a new function for the tumor suppressor protein LKB1 in a signaling cascade through which the phosphorylation and function of tau is regulated by diverse signals under physiological and pathological conditions.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
LKB-1 phosphorylates and activates PAR-1, but also phosphorylates the inactivating Ser-9 on GSK-3β and may be the elusive GSK-3β kinase activated by Wnt signaling.
“LKB-1 phosphorylates and activates PAR-1 (120,122,123), but also phosphorylates the inactivating Ser-9 on GSK-3β and may be the elusive GSK-3β kinase activated by Wnt signaling (124).”
From Functional genomic screen and network analysis reveal novel modifiers of tauopathy dissociated from tau phosphorylation (2011) · cites this paper as [123]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
1 retracted
Doglio, L. E., Kanwar, R., Jackson, G. R., Pérez, M., Ávila, J., Dingwall, C., Dotti, C. G., Fortini, M., & Feiguin, F. M. (2006) · Neuron · doi:10.1016/j.neuron.2006.03.038 · Cited by 22 · see citing works
RetractedThe Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864 · see citing works
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359 · see citing works
Triple-Transgenic Model of Alzheimer’s Disease with Plaques and Tangles
Oddo, S., Caccamo, A., Shepherd, J. D., Murphy, M. P., Golde, T. E., Kayed, R., Metherate, R., Mattson, M. P., Akbari, Y., & LaFerla, F. M. (2003) · Neuron · doi:10.1016/s0896-6273(03)00434-3 · Cited by 4,126 · cited 1× · see citing works
“Induction of amyloid pathology in these animals could promote NFT formation (Gotz et al., 2001; Lewis et al., 2001; Oddo et al., 2003).”
BackgroundGrundke-Iqbal, I., Iqbal, K., Tung, Y. C., Quinlan, M., Wisniewski, H. M., & Binder, L. I. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.13.4913 · Cited by 3,676 · see citing works
Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17
Hutton, M., Lendon, C. L., Rizzu, P., Baker, M., Froelich, S., Houlden, H., Pickering-Brown, S., Chakraverty, S., Isaacs, A., Grover, A., et al. (1998) · Nature · doi:10.1038/31508 · Cited by 3,498 · cited 1× · see citing works
“The association of mutations in tau with frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) supports that tau abnormalities can cause neurodegeneration (Foster et al., 1997; Hutton et al., 1998; Poorkaj et al., 1998; Spillantini et al., 1998).”
BackgroundLee, V. M.-Y., Goedert, M., & Trojanowski, J. Q. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.1121 · Cited by 2,480 · cited 1× · see citing works
“Several kinases and phosphatases have been shown to regulate tau phosphorylation in vitro (Lee et al., 2001).”
BackgroundShaw, R. J., Kosmatka, M., Bardeesy, N., Hurley, R. L., Witters, L. A., DePinho, R. A., & Cantley, L. C. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308061100 · Cited by 1,797 · see citing works
Hawley, S. A., Boudeau, J., Reid, J. L., Mustard, K. J., Udd, L., Mäkelä, T. P., Alessi, D. R., & Hardie, D. G. (2003) · Journal of Biology · doi:10.1186/1475-4924-2-28 · Cited by 1,666 · cited 1× · see citing works
“This LKB1 kinase complex was purified from transfected mammalian cell lines and is the kinase-active form (Hawley et al., 2003).”
BackgroundEnhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP
Lewis, J., Dickson, D. W., Lin, W.-L., Chisholm, L., Corral, A., Jones, G., Yen, S.-H., Sahara, N., Skipper, L., Yager, D., et al. (2001) · Science · doi:10.1126/science.1058189 · Cited by 1,611 · cited 3× · see citing works
“Enhanced 12E8 site phosphorylation of tau was also observed in previous studies of APP and tau double transgenic mice (Lewis et al., 2001; Perez et al., 2005), but the kinase responsible for this effect was not known.”
BackgroundFormation of Neurofibrillary Tangles in P301L Tau Transgenic Mice Induced by Aβ42 Fibrils
Götz, J., Chen, F., van Dorpe, J., & Nitsch, R. M. (2001) · Science · doi:10.1126/science.1062097 · Cited by 1,526 · cited 1× · see citing works
“Induction of amyloid pathology in these animals could promote NFT formation (Gotz et al., 2001; Lewis et al., 2001; Oddo et al., 2003).”
BackgroundMutation in the tau gene in familial multiple system tauopathy with presenile dementia
Spillantini, M. G., Murrell, J. R., Goedert, M., Farlow, M. R., Klug, A., & Ghetti, B. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.13.7737 · Cited by 1,474 · cited 1× · see citing works
“The association of mutations in tau with frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) supports that tau abnormalities can cause neurodegeneration (Foster et al., 1997; Hutton et al., 1998; Poorkaj et al., 1998; Spillantini et al., 1998).”
BackgroundA68: a Major Subunit of Paired Helical Filaments and Derivatized Forms of Normal Tau
Lee, V. M.-Y., Balin, B. J., Otvos, L., & Trojanowski, J. Q. (1991) · Science · doi:10.1126/science.1899488 · Cited by 1,418 · cited 1× · see citing works
“It becomes abnormally phosphorylated and insoluble and forms neurofibrillary tangles (NFTs) in neurodegenerative tauopathies (Grundke-Iqbal et al., 1986; Greenberg and Davies, 1990; Lee et al., 1991).”
BackgroundLKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR‐1
Lizcano, J. M., Göransson, O., Toth, R., Deak, M., Morrice, N. A., Boudeau, J., Hawley, S. A., Udd, L., Mäkelä, T. P., Hardie, D. G., et al. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600110 · Cited by 1,381 · cited 6× · see citing works
“The exact relationship between LKB1 and MARK/PAR-1 is, however, unclear because data that suggest LKB1 acting upstream or downstream of MARK/PAR-1 have both been reported (Martin and St. Johnston, 2003; Spicer et al., 2003; Brajenovic et al., 2004; Lizcano et al., 2004).”
BackgroundResultInfluentialTau is a candidate gene for chromosome 17 frontotemporal dementia
Poorkaj, P., Bird, T. D., Wijsman, E., Nemens, E., Garruto, R. M., Anderson, L., Andreadis, A., Wiederholt, W. C., Raskind, M., & Schellenberg, G. D. (1998) · Annals of Neurology · doi:10.1002/ana.410430617 · Cited by 1,374 · cited 1× · see citing works
“The association of mutations in tau with frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) supports that tau abnormalities can cause neurodegeneration (Foster et al., 1997; Hutton et al., 1998; Poorkaj et al., 1998; Spillantini et al., 1998).”
BackgroundLewis, J., McGowan, E., Rockwood, J., Melrose, H., Nacharaju, P., Van Slegtenhorst, M., Gwinn-Hardy, K., Murphy, M. P., Baker, M., Yu, X., et al. (2000) · Nature Genetics · doi:10.1038/78078 · Cited by 1,371 · cited 1× · see citing works
“Overexpression of wild-type or mutant human tau (h-tau) in mice could result in limited tangle pathology and neuronal loss, without accompanying plaque pathology (Ishihara et al., 1999; Lewis et al., 2000; Probst et al., 2000).”
BackgroundAugustinack, J. C., Schneider, A., Mandelkow, E.-M., & Hyman, B. T. (2002) · Acta Neuropathologica · doi:10.1007/s004010100423 · Cited by 998 · see citing works
Tauopathy in <i>Drosophila</i> : Neurodegeneration Without Neurofibrillary Tangles
Wittmann, C. W., Wszolek, M. F., Shulman, J. M., Salvaterra, P. M., Lewis, J., Hutton, M., & Feany, M. B. (2001) · Science · doi:10.1126/science.1062382 · Cited by 939 · cited 1× · see citing works
“Overexpression of wild-type h-tau or FTDP-17-associated h-tau(R406W) in the fly eye is toxic (Wittmann et al., 2001; Jackson et al., 2002; Nishimura et al., 2004), as indicated by a mild photoreceptor loss (Fig.”
BackgroundLucas, J. J., Hernández, F., Gómez‐Ramos, P., Morán, M. A., Hen, R., & Avila, J. (2001) · The EMBO Journal · doi:10.1093/emboj/20.1.27 · Cited by 903 · cited 1× · see citing works
“Overexpression studies using transgenic mice have implicated cyclin-dependent kinase 5 (Cdk5) and glycogen synthase kinase-3 (GSK-3 ) in tau phosphorylation, aggregation, and tangle formation (Lucas et al., 2001; Cruz et al., 2003; Noble et al., 2003).”
BackgroundDrewes, G., Ebneth, A., Preuss, U., Mandelkow, E.-M., & Mandelkow, E. (1997) · Cell · doi:10.1016/s0092-8674(00)80208-1 · Cited by 878 · cited 1× · see citing works
“Microtubule affinity regulating kinase (MARK), the mammalian homolog of PAR-1, could phosphorylate tau in vitro and was found to associate with NFT in AD brains (Drewes et al., 1997; Chin et al., 2000; Biernat et al., 2002).”
BackgroundLKB1-Dependent Signaling Pathways
Alessi, D. R., Sakamoto, K., & Bayascas, J. R. (2006) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.75.103004.142702 · Cited by 783 · cited 1× · see citing works
“LKB1 activity can also be regulated by phosphorylation and by its interaction with molecular chaperone Hsp90 (Alessi et al., 2006).”
BackgroundOddo, S., Billings, L., Kesslak, J. P., Cribbs, D. H., & LaFerla, F. M. (2004) · Neuron · doi:10.1016/j.neuron.2004.07.003 · Cited by 780 · see citing works
Greenberg, S. G., & Davies, P. J. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.15.5827 · Cited by 732 · cited 1× · see citing works
“It becomes abnormally phosphorylated and insoluble and forms neurofibrillary tangles (NFTs) in neurodegenerative tauopathies (Grundke-Iqbal et al., 1986; Greenberg and Davies, 1990; Lee et al., 1991).”
BackgroundFrontotemporal dementia and parkinsonism linked to chromosome 17: A consensus conference
Foster, N. L., Wilhelmsen, K., Sima, A. A. F., Jones, M. Z., D'Amato, C., & Gilman, S. (1997) · Annals of Neurology · doi:10.1002/ana.410410606 · Cited by 664 · cited 1× · see citing works
“The association of mutations in tau with frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) supports that tau abnormalities can cause neurodegeneration (Foster et al., 1997; Hutton et al., 1998; Poorkaj et al., 1998; Spillantini et al., 1998).”
BackgroundCruz, J. C., Tseng, H.-C., Goldman, J. A., Shih, H., & Tsai, L.-H. (2003) · Neuron · doi:10.1016/s0896-6273(03)00627-5 · Cited by 609 · cited 1× · see citing works
“Overexpression studies using transgenic mice have implicated cyclin-dependent kinase 5 (Cdk5) and glycogen synthase kinase-3 (GSK-3 ) in tau phosphorylation, aggregation, and tangle formation (Lucas et al., 2001; Cruz et al., 2003; Noble et al., 2003).”
BackgroundIshihara, T., Hong, M., Zhang, B., Nakagawa, Y., Lee, M. K., Trojanowski, J. Q., & Lee, V. M.-Y. (1999) · Neuron · doi:10.1016/s0896-6273(00)81127-7 · Cited by 564 · cited 1× · see citing works
“Overexpression of wild-type or mutant human tau (h-tau) in mice could result in limited tangle pathology and neuronal loss, without accompanying plaque pathology (Ishihara et al., 1999; Lewis et al., 2000; Probst et al., 2000).”
BackgroundCdk5 Is a Key Factor in Tau Aggregation and Tangle Formation In Vivo
Noble, W. J., Olm, V., Takata, K., Casey, E., Mary, O., Meyerson, J. L., Gaynor, K., LaFrancois, J. J., Wang, L., Kondo, T., et al. (2003) · Neuron · doi:10.1016/s0896-6273(03)00259-9 · Cited by 511 · cited 1× · see citing works
“Overexpression studies using transgenic mice have implicated cyclin-dependent kinase 5 (Cdk5) and glycogen synthase kinase-3 (GSK-3 ) in tau phosphorylation, aggregation, and tangle formation (Lucas et al., 2001; Cruz et al., 2003; Noble et al., 2003).”
BackgroundJackson, G. R., Wiedau-Pazos, M., Sang, T.-K., Wagle, N., Brown, C. A., Massachi, S., & Geschwind, D. H. (2002) · Neuron · doi:10.1016/s0896-6273(02)00706-7 · Cited by 488 · cited 1× · see citing works
“Overexpression of wild-type h-tau or FTDP-17-associated h-tau(R406W) in the fly eye is toxic (Wittmann et al., 2001; Jackson et al., 2002; Nishimura et al., 2004), as indicated by a mild photoreceptor loss (Fig.”
BackgroundGunawardena, S., & Goldstein, L. S. B. (2001) · Neuron · doi:10.1016/s0896-6273(01)00496-2 · Cited by 428 · cited 1× · see citing works
“These results suggest that NFT pathology is a downstream event resulting from amyloidinduced changes as proposed by the amyloid cascade hypothesis (Hardy and Selkoe, 2002).”
BackgroundAxonopathy and amyotrophy in mice transgenic for human four-repeat tau protein
Probst, A., Götz, J., Wiederhold, K., Tolnay, M., Mistl, C., Jaton, A., Hong, M., Ishihara, T., Lee, V., Trojanowski, J., et al. (2000) · Acta Neuropathologica · doi:10.1007/s004010051148 · Cited by 362 · cited 1× · see citing works
“Overexpression of wild-type or mutant human tau (h-tau) in mice could result in limited tangle pathology and neuronal loss, without accompanying plaque pathology (Ishihara et al., 1999; Lewis et al., 2000; Probst et al., 2000).”
BackgroundNishimura, I., Yang, Y., & Lu, B. (2004) · Cell · doi:10.1016/s0092-8674(04)00170-9 · Cited by 324 · cited 13× · see citing works
“For the analysis of neurodegeneration in the fly eye, scanning electron microscopic analysis of eye morphology and toluidine blue staining of photoreceptor neurons were performed essentially as described previously (Nishimura et al., 2004).”
BackgroundMethodInfluentialSelf-citationFerrer, I., Gómez‐Isla, T., Puig, B., Freixes, M., Ribé, E. M., Dalfó, E., & Ávila, J. (2005) · Current Alzheimer Research · doi:10.2174/1567205052772713 · Cited by 302 · cited 1× · see citing works
“There are also reports of changes of activation states of stress-induced kinases and levels of tau phosphorylation in neurons surrounding amyloid plaques in APP transgenic mice (Ferrer et al., 2005).”
BackgroundA role for Drosophila LKB1 in anterior–posterior axis formation and epithelial polarity
Martin, S. G., & Johnston, D. S. (2003) · Nature · doi:10.1038/nature01296 · Cited by 293 · see citing works
Atypical PKC Phosphorylates PAR-1 Kinases to Regulate Localization and Activity
Hurov, J., Watkins, J. L., & Piwnica-Worms, H. M. (2004) · Current Biology · doi:10.1016/j.cub.2004.04.007 · Cited by 282 · cited 2× · see citing works
“(Hurov et al., 2004), whereas MARKK and LKB1 positively reg-”
BackgroundProtein Kinase MARK/PAR-1 Is Required for Neurite Outgrowth and Establishment of Neuronal Polarity
Biernat, J., Wu, Y.-Z., Timm, T., Zheng-Fischhöfer, Q., Mandelkow, E., Meijer, L., & Mandelkow, E.-M. (2002) · Molecular Biology of the Cell · doi:10.1091/mbc.02-03-0046 · Cited by 279 · cited 1× · see citing works
“Microtubule affinity regulating kinase (MARK), the mammalian homolog of PAR-1, could phosphorylate tau in vitro and was found to associate with NFT in AD brains (Drewes et al., 1997; Chin et al., 2000; Biernat et al., 2002).”
BackgroundFischer, A., Sananbenesi, F., Pang, P. T., Lu, B., & Tsai, L.-H. (2005) · Neuron · doi:10.1016/j.neuron.2005.10.033 · Cited by 277 · cited 1× · see citing works
“This would be analogous to the opposing effects of transient versus prolonged activation of Cdk5 on synaptic plasticity and hippocampus-dependent memory (Fischer et al., 2005).”
BackgroundSelf-citationPAR-1 is a Dishevelled-associated kinase and a positive regulator of Wnt signalling
Sun, T., Lu, B., Feng, J., Reinhard, C., Jan, Y. N., Fantl, W. J., & Williams, L. T. (2001) · Nature Cell Biology · doi:10.1038/35083016 · Cited by 255 · cited 1× · see citing works
“To generate PAR-1(T408A) and PAR1(T408E) transgenics, the corresponding point mutations were introduced into a myc-tagged PAR-1 cDNA (Sun et al., 2001), using PCR-based sitedirected mutagenesis.”
MethodSelf-citationP38 MAP kinase is activated at early stages in Alzheimer's disease brain
Sun, A. (2003) · Experimental Neurology · doi:10.1016/s0014-4886(03)00180-8 · Cited by 219 · cited 1× · see citing works
“Significantly, recent findings have provided strong evidence that the p38 MAPK signaling cascade is overactivated in AD (Zhu et al., 2001; Johnson and Bailey, 2003; Sun et al., 2003).”
BackgroundNovel Genomic cDNA Hybrids Produce Effective RNA Interference in Adult Drosophila
Kalidas, S., & Smith, D. P. (2002) · Neuron · doi:10.1016/s0896-6273(02)00560-3 · Cited by 211 · cited 1× · see citing works
“To generate UAS-LKB1 RNA interference (RNAi) transgenics, genomic DNA/cDNA hybrid constructs were generated as described previously (Kalidas and Smith, 2002).”
MethodMARKK, a Ste20‐like kinase, activates the polarity‐inducing kinase MARK/PAR‐1
Timm, T., Li, X., Biernat, J., Jiao, J., Mandelkow, E., Vandekerckhove, J., & Mandelkow, E. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg447 · Cited by 198 · cited 3× · see citing works
“This latter result is consistent with previous in vitro studies of similar mutations in mammalian MARK family kinases, which caused either no or subtle activation of kinase activity in some family members (Timm et al., 2003; Lizcano et al., 2004).”
BackgroundResultBrajenovic, M., Joberty, G., Küster, B., Bouwmeester, T., & Drewes, G. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m312171200 · Cited by 188 · cited 6× · see citing works
“The exact relationship between LKB1 and MARK/PAR-1 is, however, unclear because data that suggest LKB1 acting upstream or downstream of MARK/PAR-1 have both been reported (Martin and St. Johnston, 2003; Spicer et al., 2003; Brajenovic et al., 2004; Lizcano et al., 2004).”
BackgroundResultInfluentialActivation of MKK6, an upstream activator of p38, in Alzheimer's disease
Zhu, X.-W., Rottkamp, C., Hartzler, A., Sun, Z., Takeda, A., Boux, H., Shimohama, S., Perry, G., & Smith, M. A. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00597.x · Cited by 151 · cited 1× · see citing works
“Significantly, recent findings have provided strong evidence that the p38 MAPK signaling cascade is overactivated in AD (Zhu et al., 2001; Johnson and Bailey, 2003; Sun et al., 2003).”
BackgroundIdentification and characterization of the Drosophila tau homolog
Heidary, G., & Fortini, M. (2001) · Mechanisms of Development · doi:10.1016/s0925-4773(01)00487-7 · Cited by 120 · see citing works
The p38 MAP kinase signaling pathway in Alzheimer's disease
Johnson, G. (2003) · Experimental Neurology · doi:10.1016/s0014-4886(03)00268-1 · Cited by 106 · cited 1× · see citing works
“Significantly, recent findings have provided strong evidence that the p38 MAPK signaling cascade is overactivated in AD (Zhu et al., 2001; Johnson and Bailey, 2003; Sun et al., 2003).”
BackgroundRegulation of the Wnt signalling component PAR1A by the Peutz–Jeghers syndrome kinase LKB1
Spicer, J. F., Rayter, S., Young, N., Elliott, R. J. R., Ashworth, A., & Smith, D. P. (2003) · Oncogene · doi:10.1038/sj.onc.1206669 · Cited by 99 · cited 1× · see citing works
“The exact relationship between LKB1 and MARK/PAR-1 is, however, unclear because data that suggest LKB1 acting upstream or downstream of MARK/PAR-1 have both been reported (Martin and St. Johnston, 2003; Spicer et al., 2003; Brajenovic et al., 2004; Lizcano et al., 2004).”
BackgroundElbert, M., Rossi, G., & Brennwald, P. (2004) · Molecular Biology of the Cell · doi:10.1091/mbc.e04-07-0549 · Cited by 96 · cited 1× · see citing works
“It is also possible that the PAR-1 isoform expressed from the transgenes used in this study has higher kinase activity than the other PAR-1 isoforms known to exist in vivo, resulting from the absence of a putative autoinhibitory domain at the C terminus of PAR-1 (Elbert et al., 2005).”
BackgroundChin, J., Knowles, R. B., Schneider, A., Drewes, G., Mandelkow, E., & Hyman, B. T. (2000) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/59.11.966 · Cited by 95 · cited 1× · see citing works
“Microtubule affinity regulating kinase (MARK), the mammalian homolog of PAR-1, could phosphorylate tau in vitro and was found to associate with NFT in AD brains (Drewes et al., 1997; Chin et al., 2000; Biernat et al., 2002).”
BackgroundPérez, M., Ribé, E. M., Rubio, A., Lim, F., Morán, M. A., Gómez‐Ramos, P., Ferrer, I., Isla, M. T. G., & Ávila, J. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.09.029 · Cited by 83 · cited 3× · see citing works
“Enhanced 12E8 site phosphorylation of tau was also observed in previous studies of APP and tau double transgenic mice (Lewis et al., 2001; Perez et al., 2005), but the kinase responsible for this effect was not known.”
BackgroundModulation of tau phosphorylation and intracellular localization by cellular stress
Jenkins, S. M., ZINNERMAN, M., Garner, C. C., & Johnson, G. V. W. (2000) · Biochemical Journal · doi:10.1042/bj3450263 · Cited by 63 · cited 1× · see citing works
“For this purpose, we tested the effect of high osmolarity, because tau phosphorylation at 12E8 sites was known to be sensitive to high osmolarity in cultured mammalian cells (Jenkins et al., 2000).”
BackgroundSchneider, A., Laage, R., von Ahsen, O., Fischer, A., Rossner, M. J., Scheek, S., Grünewald, S., Kuner, R., Weber, D., Krüger, C., et al. (2004) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.02228.x · Cited by 49 · cited 1× · see citing works
“The stress responsiveness of the LKB1/PAR-1 pathway was corroborated by observations in rodents that LKB1 and MARK were upregulated during focal cerebral ischemia and that MARK could be activated by electroconvulsive shock (Schneider et al., 2004; Jeon et al., 2005).”
BackgroundJeon, S., Kim, Y., Park, J., & Bae, C. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03505.x · Cited by 15 · cited 1× · see citing works
“The stress responsiveness of the LKB1/PAR-1 pathway was corroborated by observations in rodents that LKB1 and MARK were upregulated during focal cerebral ischemia and that MARK could be activated by electroconvulsive shock (Schneider et al., 2004; Jeon et al., 2005).”
Background
Flagged first, then by citations
Cited by
Sorted by citations
Drosophila Models of Neurodegenerative Diseases
Lu, B., & Vogel, H. S. (2008) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev.pathol.3.121806.151529 · Cited by 245 · see citing works
Self-citationClass IIa histone deacetylases: regulating the regulators
Martin, M., Kettmann, R., & Dequiedt, F. (2007) · Oncogene · doi:10.1038/sj.onc.1210613 · Cited by 243 · see citing works
“Indeed, the LKB1/MARK pathway is activated by high osmolarity (Wang et al., 2007) or focal cerebral ischemia (Schneider et al., 2004).”
BackgroundDrosophila melanogaster in the Study of Human Neurodegeneration
Hirth, F. (2010) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152710791556104 · Cited by 236 · see citing works
“Subsequent genetic interaction studies showed that kinasedependent phosphorylation increases tau toxicity and identified Shaggy/glycogen synthase kinase-3 [132] and MARK/Par-1 [129, 133] as key players in this process.”
BackgroundPsychosis in Alzheimer’s Disease
Murray, P. S., Kumar, S., DeMichele‐Sweet, M. A. A., & Sweet, R. A. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.08.020 · Cited by 198 · see citing works
The regulation and function of mammalian AMPK‐related kinases
Bright, N. J., Thornton, C., & Carling, D. (2009) · Acta Physiologica · doi:10.1111/j.1748-1716.2009.01971.x · Cited by 200 · see citing works
“2004) and exacerbated by LKB1 phosphorylation of PAR-1 (Wang et al. 2007).”
BackgroundThornton, C., Bright, N. J., Sastre, M., Muckett, P. J., & Carling, D. (2011) · Biochemical Journal · doi:10.1042/bj20101485 · Cited by 183 · see citing works
Activation of mTOR: a culprit of Alzheimer&rsquo;s disease?
Cai, Z., Zhou, Y., Xiao, M., Yan, L.-J., & He, W. (2015) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s75717 · Cited by 161 · see citing works
“The LKB1 complex, in response to an increase in the AMP/ATP ratio, regulates Aβ generation and the aberrant phosphorylation of tau.(47,210,211) Accordingly, it is possible that the LKB1/AMPK/mTOR signaling acts as a controller of Aβ generation and the aberrant phosphorylation of tau.”
BackgroundCell polarity signaling in the plasticity of cancer cell invasiveness
Gandalovičová, A., Vomastek, T., Rösel, D., & Brábek, J. (2016) · Oncotarget · doi:10.18632/oncotarget.7214 · Cited by 149 · see citing works
“Par4 (also known as LKB1), is likely upstream of Par1 as it has been shown to phosphorylate and activate Par1 kinase both in Drosophila and in mammals [30, 31] (Figure 3).”
BackgroundIijima-Ando, K., Sekiya, M., Maruko-Otake, A., Ohtake, Y., Suzuki, E., Lu, B., & Iijima, K. M. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002918 · Cited by 142 · see citing works
“To detect active PAR-1, a phospho-specific antibody that recognizes phosphorylated Thr408 of PAR-1, which is important for PAR-1 activity [37], was used.”
BackgroundMethodInfluentialSelf-citationWilliams, T., Courchet, J., Viollet, B., Brenman, J. E., & Polleux, F. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1013660108 · Cited by 123 · see citing works
“Our results have important implications in the context of neurodegeneration especially in light of recent results suggesting that in Drosophila, neurodegeneration induced by Par1 (MARK)-mediated Tau-hyperphosphorylation can be significantly suppressed by reducing LKB1 expression (37, 38).”
Synapses and Dendritic Spines as Pathogenic Targets in Alzheimer’s Disease
Yu, W., & Lu, B. (2012) · Neural Plasticity · doi:10.1155/2012/247150 · Cited by 119 · see citing works
“PAR-1/MARK kinases are known to be activated by APP or Aβ in Drosophila or mammalian neurons [55, 56].”
BackgroundSelf-citationAmbegaokar, S. S., & Jackson, G. R. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr432 · Cited by 113 · see citing works
“Conversely, it has been suggested that par-1 may regulate GSK-3b activity by ‘priming’ the tau protein, whereby tau phosphorylation by PAR-1 is required before GSK-3b or Cdk5 can phosphorylate tau (92).”
BackgroundInfluentialTransgenic Drosophila models of Alzheimer’s disease and tauopathies
Iijima‐Ando, K., & Iijima, K. (2009) · Brain Structure and Function · doi:10.1007/s00429-009-0234-4 · Cited by 110 · see citing works
“Because diverse stress stimuli, such as high osmolarity and human APP-induced neurotoxicity, can promote tau phosphoryla- tion and toxicity through LKB1 and PAR-1 activation (Wang et al. 2007), the LKB1/PAR-1/tau phosphorylation cascade may be involved in AD pathogenesis.”
Yu, W., Polepalli, J., Wagh, D., Rajadas, J., Malenka, R., & Lu, B. (2012) · Human Molecular Genetics · doi:10.1093/hmg/ddr576 · Cited by 103 · see citing works
“Several kinases have been shown to act upstream of PAR-1/MARK (42), including LKB1 (33).”
BackgroundResultSelf-citationAndo, K., Maruko-Otake, A., Ohtake, Y., Hayashishita, M., Sekiya, M., & Iijima, K. M. (2016) · PLOS Genetics · doi:10.1371/journal.pgen.1005917 · Cited by 105 · see citing works
Recent advances in class IIa histone deacetylases research
Asfaha, Y., Schrenk, C., Avelar, L. A. A., Hamacher, A., Pflieger, M., Kassack, M. U., & Kurz, T. (2019) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2019.115087 · Cited by 76 · see citing works
The regulation and function of the NUAK family
Sun, X., Gao, L., Chien, H.-Y., Li, W., & Zhao, J. (2013) · Journal of Molecular Endocrinology · doi:10.1530/jme-13-0063 · Cited by 76 · see citing works
Iijima-Ando, K., Zhao, L., Gatt, A., Shenton, C., & Iijima, K. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq068 · Cited by 72 · see citing works
“dMARK activity depends on its phosphorylation at Thr408 (53).”
BackgroundInfluentialGan, R., & Li, H. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms150916698 · Cited by 72 · see citing works
“can promote PAR-1 activation and tau phosphorylation in an LKB1-dependent manner [86].”
BackgroundKumar, P., Jha, N. K., Jha, S. K., Ramani, K., & Ambasta, R. K. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-140933 · Cited by 67 · see citing works
“Tumor suppressor protein LKB1 is responsible for tau phosphorylation [86, 87]”
Bioenergy sensing in the brain
Amato, S., & Man, H. (2011) · Cell Cycle · doi:10.4161/cc.10.20.17953 · Cited by 68 · see citing works
LKB1 regulates polarity remodeling and adherens junction formation in the <i>Drosophila</i> eye
Amin, N., Khan, A., St. Johnston, D., Tomlinson, I., Martin, S., Brenman, J., & McNeill, H. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812469106 · Cited by 66 · see citing works
“Although Par-1 appears to be a critical direct target of LKB1 in some tissues (1, 16), polarity establishment in the embryo is independent of Par-1 (13).”
BackgroundHuang, H.-L., Wang, S., Yin, M.-X., Dong, L., Wang, C., Wu, W., Lu, Y., Feng, M., Dai, C.-Y., Guo, X., et al. (2013) · PLoS Biology · doi:10.1371/journal.pbio.1001620 · Cited by 66 · see citing works
Hyperphosphorylated Tau is Elevated in Alzheimer's Disease with Psychosis
Murray, P. S., Kirkwood, C. M., Gray, M. C., Fish, K. N., Ikonomović, M. D., Hamilton, R. L., Kofler, J., Klunk, W. E., López, O. L., & Sweet, R. A. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-131166 · Cited by 65 · see citing works
“phosphorylation in an LKB1-dependent manner [53].”
PAR-1 kinase regulates epithelial detachment and directional protrusion of migrating border cells
McDonald, J. A., Khodyakova, A., Aranjuez, G., Dudley, C., & Montell, D. J. (2008) · Current Biology · doi:10.1016/j.cub.2008.09.041 · Cited by 63 · see citing works
“Although Drosophila LKB1 was initially reported to be downstream of PAR-1 [26], a recent study demonstrated that it phosphorylates PAR-1 in vitro and in vivo at a conserved threonine within the kinase domain [27].”
Drosophila taoControls Mushroom Body Development and Ethanol-Stimulated Behavior throughpar-1
King, I. F. G., Tsai, L. T.-Y., Pflanz, R., Voigt, A., Lee, S., Jäckle, H., Lu, B., & Heberlein, U. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.4416-10.2011 · Cited by 63 · see citing works
“These results are consistent with tao acting as a negative upstream regulator of par-1 (Wang et al., 2007) and raises the possibility that the functional relationship between these genes in Drosophila is different from that described in mammalian cells.”
BackgroundResultInfluentialSelf-citationA comprehensive systematic review of CSF proteins and peptides that define Alzheimer’s disease
Pedrero-Prieto, C. M., García‐Carpintero, S., Frontiñán-Rubio, J., Llanos-González, E., García, C. A., Alcain, F. J., Lindberg, I., Durán‐Prado, M., Peinado, J. R., & Rabanal‐Ruiz, Y. (2020) · Clinical Proteomics · doi:10.1186/s12014-020-09276-9 · Cited by 61 · see citing works
“Additionally, dysregulation of STK11 has been shown to contribute to Aβ accumulation and tauopathy AD-associated [84, 85].”
BackgroundMurphy, J. M., Korzhnev, D. M., Ceccarelli, D. F. J., Briant, D. J., Zarrine‐Afsar, A., Sicheri, F., Kay, L. E., & Pawson, T. J. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0703012104 · Cited by 65 · see citing works
Scaduto, P., Lauterborn, J. C., Cox, C. D., Fracassi, A., Zeppillo, T., Gutierrez, B. A., Keene, C. D., Crane, P. K., Mukherjee, S., Russell, W. K., et al. (2022) · Acta Neuropathologica · doi:10.1007/s00401-022-02526-0 · Cited by 68 · see citing works
“Four of the five proteins that were increased in both MCI and AD respect to control form part of the LKB1 pathway known to promote tau phosphorylation via activation of MARK2 and PAR-1 [40, 92] (Supplementary Fig.”
Investigating the Regulation of Brain-specific Kinases 1 and 2 by Phosphorylation
Bright, N. J., Carling, D., & Thornton, C. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m710381200 · Cited by 63 · see citing works
Sandí, M. J., Marshall, C. B., Balan, M., Coyaud, É., Zhou, M., Monson, D. M., Ishiyama, N., Chandrakumar, A. A., Rose, J. L., Couzens, A. L., et al. (2017) · Science Signaling · doi:10.1126/scisignal.aan3286 · Cited by 62 · see citing works
Lee, S., Wang, J.-W., Yu, W., & Lu, B. (2012) · Nature Communications · doi:10.1038/ncomms2278 · Cited by 58 · see citing works
Self-citationGailite, I., Aerne, B. L., & Tapon, N. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1505512112 · Cited by 56 · see citing works
“Stocks used in this study were FRT82B lkb1/TM6B, a gift from Jongkyeong Chung, Seoul National University, Seoul, Republic of Korea (65); UAS-lkb1, a gift from Bingwei Lu, Stanford School of Medicine, Stanford, CA (94); FRT82B lkb1/TM3 (74) and FRT42D par-1/CyO (95), gifts from Daniel St.”
Methodvan Woerden, G. M., Bos, M., de Konink, C., Distel, B., Trezza, R. A., Shur, N. E., Baranano, K. W., Mahida, S., Chassevent, A., Schreiber, A., et al. (2021) · Human Mutation · doi:10.1002/humu.24176 · Cited by 55 · see citing works
“Tao1 in Drosophila plays a role in axon guidance, and its deletion leads to malformations of the fly brain (Dulovic‐ Mahlow et al., 2019; King et al., 2011; Poon et al., 2016).”
BackgroundInfluentialMicrotubule affinity-regulating kinases are potential druggable targets for Alzheimer’s disease
Annadurai, N., Agrawal, K., Džubák, P., Hajdúch, M., & Das, V. (2017) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2574-1 · Cited by 51 · see citing works
“Interestingly, co-expression of amyloid precursor protein (APP) and MARK/Par-1 results in the phosphorylation of Par-1 Thr408 (Drosophila Par-1 Thr408 is the same conserved site as Thr208 in MARK2) and tau [46].”
BackgroundInfluentialAlzheimer's Disease and tauopathy studies in flies and worms
Wentzell, J. S., & Kretzschmar, D. (2010) · Neurobiology of Disease · doi:10.1016/j.nbd.2010.03.007 · Cited by 43 · see citing works
“suggest that the effects of APP on tau phosphorylation can be mediated by PAR-1 (Wang et al., 2007).”
BackgroundMethodThe myriad roles of Miro in the nervous system: axonal transport of mitochondria and beyond
Lee, K.-S., & Lu, B.-W. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00330 · Cited by 46 · see citing works
Self-citationAndo, K., Oka, M., Ohtake, Y., Motoki, H., Shimizu, S., Hisanaga, S., & Iijima, K. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.08.053 · Cited by 43 · see citing works
Understanding Miro GTPases: Implications in the Treatment of Neurodegenerative Disorders
Kay, L., Pienaar, I., Cooray, R., Black, G., & Soundararajan, M. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-0927-x · Cited by 40 · see citing works
JNK Pathway Activation Is Controlled by Tao/TAOK3 to Modulate Ethanol Sensitivity
Kapfhamer, D., King, I. F. G., Zou, M. E., Lim, J. P., Heberlein, U., & Wolf, F. W. (2012) · PLoS ONE · doi:10.1371/journal.pone.0050594 · Cited by 42 · see citing works
“Members of the TAO kinase family interact with both PAR-1 and the JNK pathway [23,27,30,31,90], however a direct connection of TAO kinases to the PP pathway has not been established.”
BackgroundDifferential requirements for STRAD in LKB1-dependent functions in C. elegans
Narbonne, P., Hyenne, V., Li, S., Labbé, J.-C., & Roy, R. (2010) · Development · doi:10.1242/dev.042044 · Cited by 39 · see citing works
Hannan, S. B., Dräger, N. M., Rasse, T. M., Voigt, A., & Jahn, T. R. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13532 · Cited by 38 · see citing works
Alzheimer risk gene product Pyk2 suppresses tau phosphorylation and phenotypic effects of tauopathy
Brody, A. H., Nies, S. H., Guan, F., Smith, L. M., Mukherjee, B., Salazar, S. A., Lee, S., Lam, T. K. T., & Strittmatter, S. M. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00526-y · Cited by 33 · see citing works
“Although LKB1 is both necessary and sufficient to induce Tau phosphorylation, LKB1 does not phosphorylate Tau directly [64].”
Recent advances in using Drosophila to model neurodegenerative diseases
Lu, B. (2009) · APOPTOSIS · doi:10.1007/s10495-009-0347-5 · Cited by 31 · see citing works
“Diverse stress stimuli, such as human APP-induced neurotoxicity, can promote PAR-1 activation and tau phosphorylation in an LKB1-dependent manner [101].”
BackgroundSelf-citationThe Power and Richness of Modelling Tauopathies in Drosophila
Papanikolopoulou, K., & Skoulakis, E. M. C. (2011) · Molecular Neurobiology · doi:10.1007/s12035-011-8193-1 · Cited by 28 · see citing works
“Par-1 encodes the fly ortholog of mammalian MARK, previously shown to phosphorylate Tau and regulate microtubule dynamics [91].”
BackgroundRIP2-mediated LKB1 deletion causes axon degeneration in the spinal cord and hind-limb paralysis
Sun, G., Reynolds, R., Leclerc, I., & Rutter, G. A. (2010) · Disease Models & Mechanisms · doi:10.1242/dmm.006833 · Cited by 27 · see citing works
“, 2007), and has been reported to lie downstream of LKB1 (Wang et al., 2007).”
MARK/Par1 Kinase Is Activated Downstream of NMDA Receptors through a PKA-Dependent Mechanism
Bernard, L. P., & Zhang, H. (2015) · PLoS ONE · doi:10.1371/journal.pone.0124816 · Cited by 24 · see citing works
“Since PKA is known to phosphorylate Ser431 of Par4, also known as LKB1, which the major upstream activator of Par1 [1,30,31,32], we hypothesized that NMDA receptors activate Par1 through PKA and Par4/LKB1.”
BackgroundAnimal Models of Alzheimer’s Disease
Newman, M., Kretzschmar, D., Khan, I., Chen, M., Verdile, G., & Lardelli, M. T. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-809468-6.00040-1 · Cited by 24 · see citing works
Modelling Tauopathies in Drosophila : Insights from the Fruit Fly
Cowan, C. M., Sealey, M. A., Quraishe, S., Targett, M.-T., Marcellus, K. A., Allan, D. W., & Mudher, A. K. (2011) · International Journal of Alzheimer s Disease · doi:10.4061/2011/598157 · Cited by 23 · see citing works
“This is because the coexpression of tau and APP leads to an increased tau phosphorylation at the PAR1 site 12E8, which is diminished in flies in which LKB1 is knocked down by RNAi.”
InfluentialHu, C., Kanellopoulos, A. K., Richter, M., Petersen, M., Konietzny, A., Tenedini, F. M., Hoyer, N., Cheng, L., Poon, C. L. C., Harvey, K. F., et al. (2020) · Journal of Neuroscience · doi:10.1523/jneurosci.1846-19.2020 · Cited by 20 · see citing works
“Tao kinase might be involved in phosphorylation of the MT-associated proteins Map1b and Tau via JNK and Par-1/MARK, respectively, which are important for MT stability (Kawauchi et al., 2005; Wang et al., 2007; Giacomini et al., 2018).”
BackgroundTao kinases as coordinators of actin and microtubule dynamics in developing neurons
King, I. F. G., & Heberlein, U. (2011) · Communicative & Integrative Biology · doi:10.4161/cib.16051 · Cited by 20 · see citing works
Posttranslational regulation of liver kinase B1 in human cancer
Hu, L., Liu, M., Tang, B., Li, Q., Pan, B., Xu, C. S., & Lin, H. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.104570 · Cited by 17 · see citing works
The Drosophila model system to study tau action
Trotter, M., Stephens, T. D., McGrath, J. P., & Steinhilb, M. L. (2017) · Methods in cell biology · doi:10.1016/bs.mcb.2017.06.006 · Cited by 14 · see citing works
Cassar, M., Law, A. D., Chow, E. S., Giebultowicz, J. M., & Kretzschmar, D. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00232 · Cited by 14 · see citing works
“…of synapses requires cytoskeletal changes and it has been shown that the end-binding protein 1 (EB1), needed for microtubules to grow at their plus ends (Akhmanova and Steinmetz, 2010), accumulates in loops around forming synapses (Wang et al., 2007; Stone et al., 2008; Conde and Caceres, 2009).”
BackgroundEthnicity-specific and overlapping alterations of brain hydroxymethylome in Alzheimer’s disease
Qin, L., Xu, Q., Li, Z., Chen, L., Li, Y., Yang, N., Liu, Z., Guo, J., Shen, L. H., Allen, E. G., et al. (2019) · Human Molecular Genetics · doi:10.1093/hmg/ddz273 · Cited by 14 · see citing works
“79e−21) (27) and the VEGF signaling pathway (FDR = 6.”
BackgroundGenetics of Psychosis in Alzheimer Disease
DeMichele‐Sweet, M. A. A., & Sweet, R. A. (2014) · Current Genetic Medicine Reports · doi:10.1007/s40142-014-0030-1 · Cited by 13 · see citing works
“Finally, STK11, also known as liver kinase B1, is a necessary intermediate in amyloid beta (Ab) precursor protein (APP) overexpressioninduced tau phosphorylation [35, 36].”
BackgroundAhrari, S., Mogharrab, N., & Navapour, L. (2019) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2019.1655479 · Cited by 13 · see citing works
Deng, J., Wen, C., Ding, X., Zhang, X., Hou, G., Liu, A., Xu, H., Cao, X., & Bai, Y. (2020) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.15710 · Cited by 13 · see citing works
Pleiotropic functions of TAO kinases and their dysregulation in neurological disorders
Byeon, S., & Yadav, S. (2024) · Science Signaling · doi:10.1126/scisignal.adg0876 · Cited by 9 · see citing works
Active zone proteins are transported via distinct mechanisms regulated by Par-1 kinase
Barber, K. R., Tanquary, J., Bush, K. M., Shaw, A., Woodson, M., Sherman, M. B., & Wairkar, Y. P. (2017) · PLoS Genetics · doi:10.1371/journal.pgen.1006621 · Cited by 10 · see citing works
Tao Negatively Regulates BMP Signaling During Neuromuscular Junction Development in Drosophila
Politano, S. F., Salemme, R. R., Ashley, J., López-Rivera, J. A., Bakula, T. A., Puhalla, K. A., Quinn, J. P., Juszczak, M. J., Phillip, L. K., Carrillo, R. A., et al. (2019) · Developmental Neurobiology · doi:10.1002/dneu.22681 · Cited by 10 · see citing works
“…Drosophila brains, Tao inhibits Par-1 and positively regulates the microtubule-stabilizing protein Tau during axon outgrowth and neurodegeneration (Wang et al., 2007; King et al., 2011), and there is also evidence that Tao-family kinases can directly phosphorylate Tau (Giacomini et al., 2018).”
BackgroundBarber, K. R., Hruska, M., Bush, K. M., Martinez, J. A., Fei, H., Levitan, I. B., Dalva, M. B., & Wairkar, Y. P. (2018) · Scientific Reports · doi:10.1038/s41598-018-34250-9 · Cited by 9 · see citing works
Creighton, J. R. (2011) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00358.2011 · Cited by 8 · see citing works
“Consistent with the multifunctional roles of AMPK, its actions are also linked to mechanisms involved in cell cycle regulation and protein synthesis inhibition (20).”
BackgroundBele, M. S., Gajare, K. A., & Deshmukh, A. A. (2015) · In Vitro Cellular & Developmental Biology - Animal · doi:10.1007/s11626-015-9867-1 · Cited by 8 · see citing works
Hepatocyte Surface Polarity: Its Dynamic Maintenance and Establishment
Braiterman, L. T., & Hubbard, A. L. (2009) · doi:10.1002/9780470747919.ch6 · Cited by 8 · see citing works
Kang, H., Kim, H., Kim, K., Oh, S. I., Yoon, S., Kim, J., Park, S., Cheon, Y., Her, S., Lee, M., et al. (2020) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2020.02.005 · Cited by 6 · see citing works
“Moreover, PAR-1 mediates the phosphorylation of tau, and its abnormal regulation can lead to neurodegeneration (Ando et al., 2016; Wang et al., 2007).”
BackgroundSelf-citationDrosophila CLASP regulates microtubule orientation and dendrite pruning by suppressing Par-1 kinase
Bu, S., Tang, Q., Wang, Y., Lau, S. S. Y., Yong, W. L., & Yu, F. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110887 · Cited by 6 · see citing works
Tauopathy in AD: Therapeutic Potential of MARK-4
Mumtaz, Ahmed, F., Rabbani, S. A., El‐Tanani, M., Najmi, A. K., Ali, J., & Khan, M. A. (2024) · Current Alzheimer Research · doi:10.2174/0115672050358397250126151707 · Cited by 5 · see citing works
Drosophila GSK3β promotes microtubule disassembly and dendrite pruning in sensory neurons
Dzaki, N., Bu, S., Lau, S. S. Y., Yong, W. L., & Yu, F. (2022) · Development · doi:10.1242/dev.200844 · Cited by 5 · see citing works
Loss of LKB1 Expression Decreases the Survival and Promotes Laryngeal Cancer Metastasis
He, S., Chen, Y., Wang, H., Shen, X., Sun, P., Dong, J., Liao, X.-B., Guo, G., Chen, J., Xia, L., et al. (2017) · Journal of Cancer · doi:10.7150/jca.20535 · Cited by 3 · see citing works
“Studies have revealed LKB1 interacts with some downstream signalings such as LKB1-AMPK [25], MARK/Par-1 [26], SIK [27], SNRK [28] among other pathways, the activations of them can subsequently inhibit anabolism and induce cell cycle arrest, and finally suppress cancer cell growth.”
BackgroundTau-induced mitochondrial reverse electron transport drives neurodegeneration
Li, W., Rimal, S., Bhurtel, S., Yeung, L., Lu, B. G., Grinberg, L. T., Spina, S., Cobos, I., Seeley, W. W., Guo, S., et al. (2026) · Neuron · doi:10.1016/j.neuron.2026.07.012 · Cited by 2 · see citing works
Self-citationPAR-1 in Alzheimer’s Disease: Pathophysiological Insights and Mechanistic Perspectives
Neha, Mandal, S., Sharma, V., Dhindsa, J., & Aran, K. R. (2026) · Current Medical Science · doi:10.1007/s11596-026-00175-y · Cited by 1 · see citing works
Yan, P., Jiang, W., Xue, X., Hou, T., Wang, J., Huang, D., Chen, L., Inuzuka, H., Dai, X., & Wei, W. (2026) · Cancer Letters · doi:10.1016/j.canlet.2026.218678 · Cited by 1 · see citing works
Self-citationChen, M., Kretzschmar, D., Verdile, G., & Lardelli, M. T. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-415894-8.00025-7 · Cited by 1 · see citing works
Neurodegeneration models in Drosophila
Roy, B., & Jackson, G. R. (2014) · Cambridge University Press eBooks · doi:10.1017/cbo9780511920585.012 · Cited by 1 · see citing works
Zou, D., Zuo, B., Zhu, M., Rong, L., Mao, H., Niu, H., Wang, L., & Zheng, R. Q. (2017) · Oncotarget · doi:10.18632/oncotarget.23814
“Analogously, NUAK1, also known as AMPKrelated protein kinase 5, was the downstream molecule of Akt, which participated in the classical signaling pathway with extensive consequences [63].”
BackgroundBrody, A. H., Nies, S. H., Guan, F., Smith, L. M., Mukherjee, B., Salazar, S. A., Lee, S., Lam, T. K. T., & Strittmatter, S. M. (2022) · Figshare · doi:10.6084/m9.figshare.19695711
Role of microtubule affinity‐regulating kinases in epilepsy: A novel therapeutic strategy
Xu, M., Shi, Y., Mu, X., Su, C., Wei, P., Wang, Q., Zhang, Y., Ji, S., Fu, C., Tian, J., et al. (2026) · British Journal of Pharmacology · doi:10.1111/bph.70354
“Targeting aberrant MARKs activity may prevent tau - related toxicities as evidenced in the studies by Chen et al. and Dequiedt et al. (Chen et al., 2006; Dequiedt et al., 2006; Wang et al., 2007).”
Discovery of MARK2 as a physiological kinase for PER2 in the mammalian clock
Liu, Y., Li, Y., Yu, T., Wang, T. V., Cui, Y., Zhu, C., Jia, X., Li, C., Shen, Y., Wang, Z., et al. (2026) · Cell chemical biology · doi:10.1016/j.chembiol.2026.02.007
Importance of AJ and cell polarity in the regulation of Fas signaling
Awina, H. (2019) · theses.fr (ABES) · doi:10.70675/7b0a762dzd645z4e23z9222z2abee196c637
BindingDB Entry 50008262: Recent advances in class IIa histone deacetylases research.
BindingDB (2021) · UC San Diego · doi:10.7270/q2vm4gmz
- Authors
- Wang, J.-W., Imai, Y., & Lu, B.
- Affiliations
- VA Palo Alto Health Care System (US)
- Corresponding author
- Lu, Bingwei
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2007-01-17
- Volume
- 27
- Issue
- 3
- Pages
- 574-581
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6672797
- OpenAlex
- W2051978668
- Cited by
- 80
- References
- 51
- Citations by year
- 2026: 5 · 2024: 2 · 2023: 1 · 2022: 5 · 2021: 1 · 2020: 5 · 2019: 5 · 2018: 2 · 2017: 7 · 2016: 4 · 2015: 4 · 2014: 6 · 2013: 4 · 2012: 4
- FWCI
- 3.35
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- McKnight Foundation
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (NS043167, R01NS043167)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Keywords
- LKB1, tau phosphorylation, Mark, Alzheimer's disease, tumor suppressor proteins, kinase activation, osmotic stress, amyloid precursor protein, Drosophila, neurodegeneration, signaling pathways
- MeSH terms
- AMP-Activated Protein Kinase Kinases, Animals, Drosophila, Enzyme Activation, Gene Expression Regulation, Humans, Phosphorylation, Protein Kinases, Signal Transduction, tau Proteins, Protein Serine-Threonine Kinases, Tauopathies, Tumor Suppressor Proteins, Drosophila Proteins, Animals, Genetically Modified, Glycogen Synthase Kinase 3
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
