Comprehensive Identification of PIP3-Regulated PH Domains from C. elegans to H. sapiens by Model Prediction and Live Imaging
Open accessAbstract
Phosphoinositide 3-kinase (PI3K) and its product phosphatidylinositol(3,4,5)-trisphosphate (PIP3) control cell growth, migration, and other processes by recruiting proteins with pleckstrin homology (PH) domains and possibly other domains to the plasma membrane (PM). However, previous experimental and structural work with PH domains left conflicting evidence about which ones are PIP3 regulated. Here we used live-cell confocal imaging of 130 YFP-conjugated mouse PH domains and found that 20% translocated to the PM in response to receptor-generated PIP3 production. We developed a recursive-learning algorithm to predict PIP3 regulation of 1200 PH domains from different eukaryotes and validated that it accurately predicts PIP3 regulation. Strikingly, this algorithm showed that PIP3 regulation is specified by amino acids across the PH domain, not just the PIP3-binding pocket, and must have evolved several times independently from PIP3-insensitive ancestral PH domains. Finally, our algorithm and live-cell experiments provide a functional survey of PH domains in different species, showing that PI3K regulation increased from approximately two C. elegans and four Drosophila to 40 vertebrate proteins.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
PI(3,4,5)P3 and its derivative PI(3,4)P2 interact with the lipid-binding PH domain in a range of protein effectors, resulting in their recruitment to membrane-signalling complexes and/or modulation of their activity.
“PI(3,4,5)P3 and PI(3,4)P2 interact with the lipid-binding PH-domain in a range of protein effectors, resulting in their recruitment to membrane-signalling complexes and/or modulation of their activity [78–81].”
From Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane (2020) · cites this paper as [80]
Cites
The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism
Engelman, J. A., Luo, J., & Cantley, L. C. (2006) · Nature Reviews Genetics · doi:10.1038/nrg1879 · Cited by 3,330 · see citing works
Cellular signaling by fibroblast growth factor receptors
Eswarakumar, V. P., Lax, I., & Schlessinger, J. (2005) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2005.01.001 · Cited by 1,923 · see citing works
Gao, T., Furnari, F., & Newton, A. C. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.03.008 · Cited by 906 · see citing works
PI(3,4,5)P 3 and PI(4,5)P 2 Lipids Target Proteins with Polybasic Clusters to the Plasma Membrane
Heo, W. D., Inoue, T., Park, W. S., Kim, M. L., Park, B. O., Wandless, T. J., & Meyer, T. (2006) · Science · doi:10.1126/science.1134389 · Cited by 775 · see citing works
Self-citationStauffer, T. P., Ahn, S., & Meyer, T. (1998) · Current Biology · doi:10.1016/s0960-9822(98)70135-6 · Cited by 761 · see citing works
Self-citationSpecific and high-affinity binding of inositol phosphates to an isolated pleckstrin homology domain
Lemmon, M. A., Ferguson, K. M., O'Brien, R., Sigler, P. B., & Schlessinger, J. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.23.10472 · Cited by 566 · see citing works
FAPPs control Golgi-to-cell-surface membrane traffic by binding to ARF and PtdIns(4)P
Godi, A., Campli, A. D., Konstantakopoulos, A., Tullio, G. D., Alessi, D. R., Kular, G. S., Daniele, T., Marra, P., Lucocq, J. M., & Matteis, M. A. D. (2004) · Nature Cell Biology · doi:10.1038/ncb1119 · Cited by 540 · see citing works
Signalling by PI3K isoforms: insights from gene-targeted mice
Vanhaesebroeck, B., Ali, K., Bilancio, A., Geering, B., & Foukas, L. C. (2005) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2005.02.008 · Cited by 450 · see citing works
Agonist-stimulated synthesis of phosphatidylinositol(3,4,5)-trisphosphate
Stephens, L., Jackson, T., & Hawkins, P. T. (1993) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/0167-4889(93)90072-w · Cited by 450 · see citing works
Klarlund, J. K., Guilherme, A., Holik, J. J., Virbasius, J. V., Chawla, A., & Czech, M. (1997) · Science · doi:10.1126/science.275.5308.1927 · Cited by 415 · see citing works
Mutations in the gene encoding c-Abl-binding protein SH3BP2 cause cherubism
Ueki, Y., Tiziani, V., Santanna, C., Fukai, N., Maulik, C., Garfinkle, J., Ninomiya, C., doAmaral, C., Peters, H., Habal, M. B., et al. (2001) · Nature Genetics · doi:10.1038/88832 · Cited by 382 · see citing works
Genome-Wide Analysis of Membrane Targeting by S. cerevisiae Pleckstrin Homology Domains
Yu, J. W., Mendrola, J. M., Audhya, A., Singh, S. M., Keleti, D., DeWald, D. B., Murray, D., Emr, S. D., & Lemmon, M. A. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00083-8 · Cited by 338 · see citing works
Myosin-X is a molecular motor that functions in filopodia formation
Bohil, A. B., Robertson, B. W., & Cheney, R. E. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0602443103 · Cited by 337 · see citing works
Protein kinase B/Akt at a glance
Fayard, E., Tintignac, L. A. J., Baudry, A., & Hemmings, B. A. (2005) · Journal of Cell Science · doi:10.1242/jcs.02724 · Cited by 336 · see citing works
Structural Basis for Discrimination of 3-Phosphoinositides by Pleckstrin Homology Domains
Ferguson, K. M., Kavran, J. M., Sankaran, V. G., Fournier, E., Isakoff, S. J., Skolnik, E. Y., & Lemmon, M. A. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)00037-x · Cited by 333 · see citing works
PI 3‐kinase: structural and functional analysis of intersubunit interactions.
Dhand, R., Hara, K., Hiles, I., Bax, B. D., Gout, I. T., Panayotou, G., Fry, M., Yonezawa, K., Kasuga, M., & Waterfield, M. D. (1994) · The EMBO Journal · doi:10.1002/j.1460-2075.1994.tb06289.x · Cited by 329 · see citing works
Isakoff, S. J., Cardozo, T., Andreev, J., Li, Z., Ferguson, K. M., Abagyan, R., Lemmon, M. A., Aronheim, A., & Skolnik, E. Y. (1998) · The EMBO Journal · doi:10.1093/emboj/17.18.5374 · Cited by 324 · see citing works
THOMAS, C. C., Deák, M., Alessi, D. R., & van Aalten, D. M. F. (2002) · Current Biology · doi:10.1016/s0960-9822(02)00972-7 · Cited by 300 · see citing works
Pleckstrin homology (PH) domains and phosphoinositides
Lemmon, M. A. (2007) · Biochemical Society Symposium · doi:10.1042/bss0740081 · Cited by 298 · see citing works
Structural Basis of 3-Phosphoinositide Recognition by Pleckstrin Homology Domains
Lietzke, S. E., Bose, S., Cronin, T., Klarlund, J. K., Chawla, A., Czech, M., & Lambright, D. G. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)00038-1 · Cited by 266 · see citing works
DOWLER, S., Kular, G. S., & Alessi, D. R. (2002) · Science s STKE · doi:10.1126/stke.2002.129.pl6 · Cited by 249 · see citing works
Hyvönen, M., & Saraste, M. (1997) · The EMBO Journal · doi:10.1093/emboj/16.12.3396 · Cited by 241 · see citing works
Pleckstrin homology (PH) domains and phosphoinositides
Lemmon, M. A. (2007) · Biochemical Society Symposia · doi:10.1042/bss2007c08 · Cited by 233 · see citing works
Kontos, C. D., Stauffer, T. P., Yang, W.-P., York, J. D., Huang, L., Blanar, M. A., Meyer, T., & Peters, K. G. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.7.4131 · Cited by 226 · see citing works
Self-citationCôté, J., Motoyama, A. B., Bush, J., & Vuori, K. (2005) · Nature Cell Biology · doi:10.1038/ncb1280 · Cited by 222 · see citing works
Structural insights into the regulation of PDK1 by phosphoinositides and inositol phosphates
Komander, D., Fairservice, A., Deák, M., Kular, G. S., Prescott, A. R., Downes, C. P., Safrany, S. T., Alessi, D. R., & van Aalten, D. M. F. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600379 · Cited by 170 · see citing works
THOMAS, C. C., DOWLER, S., Deák, M., Alessi, D. R., & van Aalten, D. M. F. (2001) · Biochemical Journal · doi:10.1042/0264-6021:3580287 · Cited by 98 · see citing works
Human CNK1 Acts as a Scaffold Protein, Linking Rho and Ras Signal Transduction Pathways
Jaffe, A. B., Aspenström, P., & Hall, A. K. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.4.1736-1746.2004 · Cited by 93 · see citing works
Guanine nucleotide exchange factors of the cytohesin family and their roles in signal transduction
Kolanus, W. (2007) · Immunological Reviews · doi:10.1111/j.1600-065x.2007.00542.x · Cited by 89 · see citing works
A novel phosphatidylinositol(3,4,5)P3 pathway in fission yeast
Mitra, P., Zhang, Y., Rameh, L. E., Ivshina, M. P., McCollum, D., Nunnari, J. J., Hendricks, G. M., Kerr, M. L., Field, S. J., Cantley, L. C., et al. (2004) · The Journal of Cell Biology · doi:10.1083/jcb.200404150 · Cited by 84 · see citing works
Tec Kinases in T Cell and Mast Cell Signaling
Felices, M., Falk, M., Kosaka, Y., & Berg, L. J. (2007) · Advances in immunology · doi:10.1016/s0065-2776(06)93004-1 · Cited by 76 · see citing works
Update: PtdIns(3,4,5)P 3 Gets Its Message Across
Hemmings, B. A. (1997) · Science · doi:10.1126/science.277.5325.534 · Cited by 74 · see citing works
Oxysterol binding protein and its homologues: new regulatory factors involved in lipid metabolism
Olkkonen, V. M. (2004) · Current Opinion in Lipidology · doi:10.1097/00041433-200406000-00013 · Cited by 51 · see citing works
Orrico, A., Galli, L., Falciani, M., Bracci, M., Cavaliere, M. L., Rinaldi, M. M., Musacchio, A., & Sorrentino, V. (2000) · FEBS Letters · doi:10.1016/s0014-5793(00)01857-3 · Cited by 42 · see citing works
Pleckstrin 2, a Widely Expressed Paralog of Pleckstrin Involved in Actin Rearrangement
Hu, M. H., Bauman, E. M., Roll, R. L., Yeilding, N. M., & Abrams, C. S. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.31.21515 · Cited by 42 · see citing works
Role of the adaptor proteins Bam32, TAPP1 and TAPP2 in lymphocyte activation
Allam, A., & Marshall, A. J. (2004) · Immunology Letters · doi:10.1016/j.imlet.2004.09.019 · Cited by 40 · see citing works
Effect of Fgd1 on Cortactin in Arp2/3 Complex-Mediated Actin Assembly
Kim, K., Hou, P., Gorski, J. L., & Cooper, J. A. (2004) · Biochemistry · doi:10.1021/bi036173t · Cited by 38 · see citing works
BOTTOMLEY, J. R., Reynolds, J. S., Lockyer, P. J., & Cullen, P. J. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.9179 · Cited by 31 · see citing works
Sun, B., & Firtel, R. (2003) · Molecular Biology of the Cell · doi:10.1091/mbc.e02-08-0550 · Cited by 23 · see citing works
The Alliance for Cellular Signaling Plasmid Collection
Zavzavadjian, J. R., Couture, S., Park, W. S., Whalen, J. H., Lyon, S., Lee, G., Fung, E., Mi, Q., Liu, J., Wall, E. A., et al. (2006) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m600437-mcp200 · Cited by 14 · see citing works
Self-citationStructural determinants of LL5β subcellular localisation and association with filamin C
Paranavitane, V., Stephens, L., & Hawkins, P. T. (2006) · Cellular Signalling · doi:10.1016/j.cellsig.2006.10.007 · Cited by 13 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
PI3K isoforms in cell signalling and vesicle trafficking
Bilanges, B., Posor, Y., & Vanhaesebroeck, B. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0129-z · Cited by 520 · see citing works
Signaling by the Phosphoinositide 3-Kinase Family in Immune Cells
Okkenhaug, K. (2013) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032712-095946 · Cited by 446 · see citing works
PI3K signaling in cancer: beyond AKT
Lien, E. C., Dibble, C. C., & Toker, A. (2017) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2017.02.007 · Cited by 446 · see citing works
Mechanisms of PTEN loss in cancer: It’s all about diversity
Garcia, V. A., Tawil, Y., Wise, H. M., & Leslie, N. R. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.02.001 · Cited by 407 · see citing works
Jo, H., Mondal, S., Tan, D. J., Nagata, E., Takizawa, S., Sharma, A. K., Hou, Q., Shanmugasundaram, K., Prasad, A., Tung, J. K., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1202810109 · Cited by 368 · see citing works
Interactome map uncovers phosphatidylserine transport by oxysterol-binding proteins
Maeda, K., Anand, K., Chiapparino, A., Kumar, A., Poletto, M., Kaksonen, M., & Gavin, A. (2013) · Nature · doi:10.1038/nature12430 · Cited by 338 · see citing works
Phosphatidylinositol 3-kinase, growth disorders, and cancer
Goncalves, M. D., Hopkins, B. D., & Cantley, L. C. (2018) · New England Journal of Medicine · doi:10.1056/nejmra1704560 · Cited by 327 · see citing works
Lin, A., Hu, Q., Li, C., Xing, Z., Ma, G., Wang, C., Li, J., Yin, Y., Yao, J., Liang, K., et al. (2017) · Nature Cell Biology · doi:10.1038/ncb3473 · Cited by 263 · see citing works
Filopodia and adhesion in cancer cell motility
Arjonen, A., Kaukonen, R., & Ivaska, J. (2011) · Cell Adhesion & Migration · doi:10.4161/cam.5.5.17723 · Cited by 256 · see citing works
Regulation and Functions of Diacylglycerol Kinases
Shulga, Y. V., Topham, M. K., & Epand, R. M. (2011) · Chemical Reviews · doi:10.1021/cr1004106 · Cited by 233 · see citing works
The present and future of PI3K inhibitors for cancer therapy
Castel, P., Toska, E., Engelman, J. A., & Scaltriti, M. (2021) · Nature Cancer · doi:10.1038/s43018-021-00218-4 · Cited by 222 · see citing works
Conceptual Evolution of Cell Signaling
Nair, A., Chauhan, P. S., Saha, B., & Kubatzky, K. F. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20133292 · Cited by 218 · see citing works
Costa, C., Ebi, H., Martini, M., Beausoleil, S. A., Faber, A. C., Jakubik, C. T., Huang, A., Wang, Y., Nishtala, M. V., Hall, B. A., et al. (2014) · Cancer Cell · doi:10.1016/j.ccell.2014.11.007 · Cited by 205 · see citing works
Prostate cancer, PI3K, PTEN and prognosis
Wise, H. M., Hermida, M. A., & Leslie, N. R. (2017) · Clinical Science · doi:10.1042/cs20160026 · Cited by 203 · see citing works
Spatiotemporal Control of Fibroblast Growth Factor Receptor Signals by Blue Light
Kim, N., Kim, J. M., Lee, M., Kim, C. Y., Chang, K.-Y., & Heo, W. D. (2014) · Chemistry & Biology · doi:10.1016/j.chembiol.2014.05.013 · Cited by 189 · see citing works
The systematic analysis of protein–lipid interactions comes of age
Saliba, A., Vonkova, I., & Gavin, A. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm4080 · Cited by 186 · see citing works
PTEN-opathies: from biological insights to evidence-based precision medicine
Yehia, L., Ngeow, J. Y. Y., & Eng, C. (2019) · Journal of Clinical Investigation · doi:10.1172/jci121277 · Cited by 178 · see citing works
Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane
Katan, M., & Cockcroft, S. (2020) · Essays in Biochemistry · doi:10.1042/ebc20200041 · Cited by 176 · see citing works
Conditional Peripheral Membrane Proteins: Facing up to Limited Specificity
Moravcevic, K., Oxley, C. L., & Lemmon, M. A. (2011) · Structure · doi:10.1016/j.str.2011.11.012 · Cited by 167 · see citing works
A systematic screen for protein–lipid interactions in Saccharomyces cerevisiae
Gallego, O., Betts, M. J., Gvozdenovic‐Jeremic, J., Maeda, K., Matetzki, C., Aguilar‐Gurrieri, C., Beltrán-Álvarez, P., Bonn, S., Fernández‐Tornero, C., Jensen, L. J., et al. (2010) · Molecular Systems Biology · doi:10.1038/msb.2010.87 · Cited by 160 · see citing works
Non-genomic loss of PTEN function in cancer: not in my genes
Leslie, N. R., & Foti, M. (2011) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2010.12.005 · Cited by 156 · see citing works
Myosin-X: a MyTH-FERM myosin at the tips of filopodia
Kerber, M. L., & Cheney, R. E. (2011) · Journal of Cell Science · doi:10.1242/jcs.023549 · Cited by 151 · see citing works
Vav family exchange factors: an integrated regulatory and functional view
Bustelo, X. R. (2014) · Small GTPases · doi:10.4161/21541248.2014.973757 · Cited by 143 · see citing works
Miao, B., Skidan, I. N., Yang, J., Lugovskoy, A. A., Reibarkh, M., Long, K., Brazell, T., Durugkar, K. A., Maki, J. L., Ramana, C. V., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1004522107 · Cited by 136 · see citing works
Optimal Experimental Design for Parameter Estimation of a Cell Signaling Model
Bandara, S., Schlöder, J. P., Eils, R., Bock, H. G., & Meyer, T. (2009) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000558 · Cited by 135 · see citing works
Self-citationTurning Off AKT: PHLPP as a Drug Target
Newton, A. C., & Trotman, L. C. (2014) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-011112-140338 · Cited by 131 · see citing works
Lipid binding domains: more than simple lipid effectors
Stahelin, R. V. (2008) · Journal of Lipid Research · doi:10.1194/jlr.r800078-jlr200 · Cited by 127 · see citing works
Alcantara, D., Timms, A. E., Gripp, K. W., Baker, L., Park, K., Collins, S., Cheng, C. V., Stewart, F. A., Mehta, S. G., Saggar, A. K., et al. (2017) · Brain · doi:10.1093/brain/awx203 · Cited by 113 · see citing works
Small-Molecule Inhibitors of the Pi3K Signaling Network
McNamara, C. R., & Degterev, A. (2011) · Future Medicinal Chemistry · doi:10.4155/fmc.11.12 · Cited by 113 · see citing works
Suppression of survival signalling pathways by the phosphatase PHLPP
O’Neill, A., Niederst, M. J., & Newton, A. C. (2012) · FEBS Journal · doi:10.1111/j.1742-4658.2012.08537.x · Cited by 107 · see citing works
Detection and manipulation of phosphoinositides
Idevall‐Hagren, O., & Camilli, P. V. D. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2014.12.008 · Cited by 104 · see citing works
Fox, E. M., Kuba, M. G., Miller, T. W., Davies, B. R., & Arteaga, C. L. (2013) · Breast Cancer Research · doi:10.1186/bcr3449 · Cited by 90 · see citing works
The discovery of modular binding domains: building blocks of cell signalling
Mayer, B. J. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm4068 · Cited by 89 · see citing works
PtdIns(3,4,5)<i>P</i>3 is a regulator of myosin-X localization and filopodia formation
Plantard, L., Arjonen, A., Lock, J. G., Nurani, G., Ivaska, J., & Strömblad, S. (2010) · Journal of Cell Science · doi:10.1242/jcs.069609 · Cited by 84 · see citing works
Hammond, G. R. V., Sim, Y., Lagnado, L., & Irvine, R. F. (2009) · The Journal of Cell Biology · doi:10.1083/jcb.200809073 · Cited by 82 · see citing works
Class I PI 3-kinases: Function and evolution
Kriplani, N., Hermida, M. A., Brown, E. R., & Leslie, N. R. (2015) · Advances in Biological Regulation · doi:10.1016/j.jbior.2015.05.002 · Cited by 81 · see citing works
Regulation of immune cell development through soluble inositol-1,3,4,5-tetrakisphosphate
Sauer, K., & Cooke, M. P. (2010) · Nature reviews. Immunology · doi:10.1038/nri2745 · Cited by 80 · see citing works
Jungmichel, S., Sylvestersen, K. B., Choudhary, C., Nguyen, S., Mann, M., & Nielsen, M. L. (2014) · Cell Reports · doi:10.1016/j.celrep.2013.12.038 · Cited by 80 · see citing works
Warfel, N. A., & Newton, A. C. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.r111.318675 · Cited by 79 · see citing works
Regulation of PI3K by PKC and MARCKS: Single-Molecule Analysis of a Reconstituted Signaling Pathway
Ziemba, B. P., Burke, J. E., Masson, G. R., Williams, R. L., & Falke, J. J. (2016) · Biophysical Journal · doi:10.1016/j.bpj.2016.03.001 · Cited by 76 · see citing works
PDK1 promotes tumor growth and metastasis in a spontaneous breast cancer model
Du, J., Yang, M., Chen, S.-H., Li, D., Chang, Z., & Dong, Z. (2015) · Oncogene · doi:10.1038/onc.2015.393 · Cited by 75 · see citing works
Moving in the right direction: How eukaryotic cells migrate along chemical gradients
Cai, H., & Devreotes, P. N. (2011) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2011.07.020 · Cited by 74 · see citing works
Redefining the specificity of phosphoinositide-binding by human PH domain-containing proteins
Singh, N., Reyes‐Ordoñez, A., Compagnone, M. A., Moreno, J. F., Leslie, B. J., Ha, T., & Chen, J. (2021) · Nature Communications · doi:10.1038/s41467-021-24639-y · Cited by 67 · see citing works
Mandal, K., Aroush, D. R.-B., Graber, Z. T., Wu, B., Park, C. Y., Fredberg, J., Guo, W., Baumgart, T., & Janmey, P. A. (2018) · ACS Nano · doi:10.1021/acsnano.8b05286 · Cited by 67 · see citing works
Chen, Y., Sheng, R., Källberg, M., Silkov, A., Tun, M. P., Bhardwaj, N., Kurilova, S., Hall, R. A., Honig, B. H., Lu, H. J., et al. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.02.012 · Cited by 66 · see citing works
Lipid Cooperativity as a General Membrane-Recruitment Principle for PH Domains
Vonkova, I., Saliba, A., Deghou, S., Anand, K., Ceschia, S., Doerks, T., Haribowo, A. G., Kugler, K., Maeda, K., Rybin, V., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.07.054 · Cited by 64 · see citing works
Gokhale, N., Zaremba, A., Janoshazi, A. K., Weaver, J. D., & Shears, S. B. (2013) · Biochemical Journal · doi:10.1042/bj20121528 · Cited by 64 · see citing works
Guittard, G. C., Gérard, A., Dupuis-Coronas, S., Tronchère, H., Mortier, E., Favre, C., Olive, D., Zimmermann, P., Payrastre, B., & Nunès, J. A. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0804172 · Cited by 63 · see citing works
Yamamoto, E., Domański, J., Naughton, F. B., Best, R. B., Kalli, A. C., Stansfeld, P. J., & Sansom, M. S. P. (2020) · Science Advances · doi:10.1126/sciadv.aay5736 · Cited by 62 · see citing works
Protein Kinase C Quality Control by Phosphatase PHLPP1 Unveils Loss-of-Function Mechanism in Cancer
Baffi, T. R., Van, A. N., Zhao, W., Mills, G. B., & Newton, A. C. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.02.018 · Cited by 56 · see citing works
PAQR3 Modulates Insulin Signaling by Shunting Phosphoinositide 3-Kinase p110α to the Golgi Apparatus
Wang, X., Wang, L., Zhu, L., Pan, Y., Xiao, F., Liu, W., Wang, Z., Guo, F., Liu, Y., Thomas, W. G., et al. (2012) · Diabetes · doi:10.2337/db12-0244 · Cited by 55 · see citing works
Membrane and Protein Interactions of the Pleckstrin Homology Domain Superfamily
Lenoir, M., Kufareva, I., Abagyan, R. A., & Overduin, M. (2015) · Membranes · doi:10.3390/membranes5040646 · Cited by 54 · see citing works
Novel Inhibitors of AKT: Assessment of a Different Approach Targeting the Pleckstrin Homology Domain
Meuillet, E. J. (2011) · Current Medicinal Chemistry · doi:10.2174/092986711796011292 · Cited by 52 · see citing works
Vu, N., Kim, M., Stephenson, D., MacKnight, H. P., & Chalfant, C. E. (2022) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-22-0085 · Cited by 51 · see citing works
Class I Phosphoinositide 3-Kinase PIK3CA/p110α and PIK3CB/p110β Isoforms in Endometrial Cancer
Gavgani, F. M., Arnesen, V. S., Jacobsen, R. G., Krakstad, C., Høivik, E. A., & Lewis, A. E. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19123931 · Cited by 50 · see citing works
Gokhale, N., Zaremba, A., & Shears, S. B. (2011) · Biochemical Journal · doi:10.1042/bj20101437 · Cited by 49 · see citing works
Ankyrin repeat-containing N-Ank proteins shape cellular membranes
Wolf, D., Hofbrucker-MacKenzie, S. A., Izadi, M., Seemann, E. A., Steiniger, F., Schwintzer, L., Koch, D. C., Kessels, M. M., & Qualmann, B. (2019) · Nature Cell Biology · doi:10.1038/s41556-019-0381-7 · Cited by 49 · see citing works
Exogenous Application of dsRNA for the Control of Viruses in Cucurbits
Delgado-Martín, J., Ruiz, L., Janssen, D., & Velasco, L. (2022) · Frontiers in Plant Science · doi:10.3389/fpls.2022.895953 · Cited by 47 · see citing works
Diacylglycerol Kinases: Regulated Controllers of T Cell Activation, Function, and Development
Joshi, R. P., & Koretzky, G. A. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms14046649 · Cited by 47 · see citing works
Liao, X., Buggey, J., & Kimmel, A. R. (2010) · Journal of Cell Science · doi:10.1242/jcs.064022 · Cited by 47 · see citing works
Macropinosomes as units of signal transduction
Swanson, J. A., & Yoshida, S. (2018) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2018.0157 · Cited by 47 · see citing works
Emerging methodologies to investigate lipid–protein interactions
Scott, J. L., Musselman, C. A., Adu‐Gyamfi, E., Kutateladze, T. G., & Stahelin, R. V. (2012) · Integrative Biology · doi:10.1039/c2ib00143h · Cited by 45 · see citing works
Function and Regulation of Protein Kinase D in Oxidative Stress: A Tale of Isoforms
Cobbaut, M., & Lint, J. V. (2018) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2018/2138502 · Cited by 45 · see citing works
Polyphosphoinositide-Binding Domains: Insights from Peripheral Membrane and Lipid-Transfer Proteins
Pemberton, J. G., & Balla, T. (2018) · Advances in experimental medicine and biology · doi:10.1007/5584_2018_288 · Cited by 44 · see citing works
Durrant, T. N., Hutchinson, J. L., Heesom, K. J., Anderson, K. E., Stephens, L., Hawkins, P. T., Marshall, A. J., Moore, S., & Hers, I. (2017) · Blood Advances · doi:10.1182/bloodadvances.2017005173 · Cited by 41 · see citing works
Lipid-dependent Akt-ivity: where, when, and how
Siess, K. M., & Leonard, T. A. (2019) · Biochemical Society Transactions · doi:10.1042/bst20190013 · Cited by 40 · see citing works
Kim, K., Kim, J., Sung, J. H., Suh, K. J., Lee, J. Y., Kim, S. H., Lee, J., Kim, J. W., Kim, Y. J., Kim, J. H., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-68998-w · Cited by 40 · see citing works
Park, H. H., Hwang, W., Ham, S., Kim, E., Altıntaş, Ö., Park, S., Son, H. G., Lee, Y., Lee, D.-Y., Heo, W. D., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-25920-w · Cited by 40 · see citing works
Zhang, P., Wang, Y., Sesaki, H., & Iijima, M. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1006153107 · Cited by 40 · see citing works
Müller, R., Kojic, A., Citir, M., & Schultz, C. (2021) · Angewandte Chemie International Edition · doi:10.1002/anie.202103599 · Cited by 39 · see citing works
Asanov, A. N., Sampieri, A., Moreno, C. M., Pacheco, J. E., Salgado-Aguayo, A. R., Sherry, R., & Vaca, L. A. (2014) · Cell Calcium · doi:10.1016/j.ceca.2014.10.011 · Cited by 38 · see citing works
Lipid and Protein Co-Regulation of PI3K Effectors Akt and Itk in Lymphocytes
Wang, X., Hills, L. B., & Huang, Y. H. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00117 · Cited by 38 · see citing works
Distinct inactivation of PI3K signalling by PTEN and 5-phosphatases
Leslie, N. R., Dixon, M. J., Schenning, M., Gray, A., & Batty, I. H. (2011) · Advances in Biological Regulation · doi:10.1016/j.advenzreg.2011.09.010 · Cited by 37 · see citing works
Indarte, M., Puentes, R., Maruggi, M., Ihle, N. T., Grandjean, G. V., Scott, M. J., Ahmed, Z., Meuillet, E. J., Zhang, S., Lemos, R., et al. (2019) · Cancer Research · doi:10.1158/0008-5472.can-18-2372 · Cited by 37 · see citing works
Ziemba, B. P., Pilling, C., Calleja, V., Larijani, B., & Falke, J. J. (2013) · Biochemistry · doi:10.1021/bi400488f · Cited by 37 · see citing works
Johansen, K. H., Golec, D. P., Huang, B., Park, C., Thomsen, J. H., Preite, S., Cannons, J. L., Garçon, F., Schrom, E. C., Courrèges, C. J. F., et al. (2022) · Science Signaling · doi:10.1126/scisignal.abl9169 · Cited by 36 · see citing works
Ortutay, C., Nore, B. F., Vihinen, M., & Smith, C. I. E. (2008) · Advances in genetics · doi:10.1016/s0065-2660(08)00803-1 · Cited by 34 · see citing works
Phosphoinositides Differentially Regulate Protrudin Localization through the FYVE Domain
Gil, J.-E., Kim, E., Kim, I.-S., Ku, B., Park, W. S., Oh, B., Ryu, S. H., Cho, W., & Heo, W. D. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.419127 · Cited by 34 · see citing works
Self-citationAyling, L. J., Briddon, S. J., Halls, M. L., Hammond, G. R. V., Vaca, L. A., Pacheco, J. E., Hill, S. J., & Cooper, D. M. F. (2012) · Journal of Cell Science · doi:10.1242/jcs.091090 · Cited by 34 · see citing works
Campa, F., Yoon, H., Ha, V. L., Szentpétery, Z., Balla, T., & Randazzo, P. A. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.028266 · Cited by 33 · see citing works
PHLPPing the Script: Emerging Roles of PHLPP Phosphatases in Cell Signaling
Baffi, T. R., Cohen‐Katsenelson, K., & Newton, A. C. (2020) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-031820-122108 · Cited by 32 · see citing works
Two cooperative binding sites sensitize PI(4,5)P 2 recognition by the tubby domain
Thallmair, V., Schultz, L., Zhao, W., Marrink, . J., Oliver, D., & Thallmair, S. (2022) · Science Advances · doi:10.1126/sciadv.abp9471 · Cited by 32 · see citing works
Phosphoinositide 3-kinase p110γ in immunity
Costa, C., Conte, E., & Hirsch, E. (2011) · IUBMB Life · doi:10.1002/iub.516 · Cited by 32 · see citing works
Crucial Role of the SH2B1 PH Domain for the Control of Energy Balance
Flores, A., Argetsinger, L. S., Stadler, L. K. J., Malaga, A. E., Vander, P. B., DeSantis, L. C., Joe, R. M., Cline, J. M., Keogh, J. M., Henning, E., et al. (2019) · Diabetes · doi:10.2337/db19-0608 · Cited by 31 · see citing works
Manna, P., & Jain, S. K. (2013) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-013-1714-7 · Cited by 31 · see citing works
Development of sulfonamide AKT PH domain inhibitors
Ahad, A. M., Song, Z., Du‐Cuny, L., Moses, S. A., Zhou, L., Zhang, S., Powis, G., Meuillet, E. J., & Mash, E. A. (2011) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2011.01.049 · Cited by 30 · see citing works
The PI(3)P interactome from a colon cancer cell
Catimel, B., Kapp, E. A., Yin, M.-X., Gregory, M. A., Wong, L. S. ‐., Condron, M. M., Church, N., Kershaw, N. J., Holmes, A. B., & Burgess, A. W. (2013) · Journal of Proteomics · doi:10.1016/j.jprot.2013.01.031 · Cited by 30 · see citing works
Akt and SGK protein kinases are required for efficient feeding by macropinocytosis
Williams, T. D., Peak‐Chew, S., Paschke, P., & Kay, R. R. (2019) · Journal of Cell Science · doi:10.1242/jcs.224998 · Cited by 30 · see citing works
Ivarsson, Y., Wawrzyniak, A. M., Kashyap, R. S., Polanowska, J., Betzi, S., Lembo, F., Vermeiren, E., Chiheb, D., Lenfant, N., Morelli, X., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0054581 · Cited by 29 · see citing works
Noh, J., Wende, A. R., Olsen, C. D., Kim, B. J., Bevins, J., Zhu, Y., Zhang, Q., Riehle, C., & Abel, E. D. (2015) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2015.10.015 · Cited by 28 · see citing works
Computational Analysis of the Binding Specificities of PH Domains
Jiang, Z., Liang, Z. T., Shen, B., & Hu, G. (2015) · BioMed Research International · doi:10.1155/2015/792904 · Cited by 28 · see citing works
Leep1 interacts with PIP3 and the Scar/WAVE complex to regulate cell migration and macropinocytosis
Yang, Y., Li, D., Chao, X., Singh, S. P., Thomason, P. A., Yan, Y., Dong, M., Li, L., Insall, R. H., & Cai, H. (2021) · The Journal of Cell Biology · doi:10.1083/jcb.202010096 · Cited by 28 · see citing works
ARF6, PI3-kinase and host cell actin cytoskeleton in Toxoplasma gondii cell invasion
da Silva, C. V., da Silva, E. A., Cruz, M. C., Chavrier, P., & Mortara, R. A. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.11.108 · Cited by 28 · see citing works
Inhibition of cell migration by PITENINs: the role of ARF6
Miao, B., Skidan, I. N., Yang, J. L., You, Z., Fu, X., Famulok, M., Schaffhausen, B. S., Torchilin, V. P., Yuan, J., & Degterev, A. (2011) · Oncogene · doi:10.1038/onc.2011.593 · Cited by 27 · see citing works
Yan, L., Hou, C., Liu, J., Wang, Y., Zeng, C., Yu, J., Zhou, T., Zhou, Q., Duan, S., & Xiong, W. (2023) · Science China Life Sciences · doi:10.1007/s11427-022-2314-8 · Cited by 26 · see citing works
Dok-4 Is a Novel Negative Regulator of T Cell Activation
Gérard, A., Ghiotto, M., Fos, C., Guittard, G. C., Compagno, D., Galy, A. H. M., Lemay, S., Olive, D., & Nunès, J. A. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0802203 · Cited by 26 · see citing works
Pilling, C., Landgraf, K. E., & Falke, J. J. (2011) · Biochemistry · doi:10.1021/bi2011306 · Cited by 26 · see citing works
Increased PIP3 activity blocks nanoparticle mRNA delivery
Paunovska, K., Sanchez, A. D. S., Foster, M. T., Loughrey, D., Blanchard, E. L., Islam, F. Z., Gan, Z., Mantalaris, A., Santangelo, P. J., & Dahlman, J. E. (2020) · Science Advances · doi:10.1126/sciadv.aba5672 · Cited by 26 · see citing works
Barrows, D., Schoenfeld, S., Hodakoski, C., Silkov, A., Honig, B. H., Couvillon, A. D., Shymanets, A., Nürnberg, B., Asara, J. M., & Parsons, R. E. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.668244 · Cited by 25 · see citing works
Zhang, Y., Cao, F., Zhou, Y., Feng, Z., Sit, B. H. M., Krendel, M., & Yu, C. (2019) · Molecular Biology of the Cell · doi:10.1091/mbc.e18-06-0398 · Cited by 24 · see citing works
- Authors
- Park, W. S., Do Heo, W., Whalen, J. H., O'Rourke, N. A., Bryan, H. M., Meyer, T., & Teruel, M. N.
- Affiliations
- Stanford University (US)
- Corresponding author
- Teruel, Mary N.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2008-05
- Volume
- 30
- Issue
- 3
- Pages
- 381-392
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC3523718
- OpenAlex
- W2038641650
- Cited by
- 167
- References
- 41
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 3 · 2023: 6 · 2022: 8 · 2021: 8 · 2020: 9 · 2019: 13 · 2018: 6 · 2017: 6 · 2016: 4 · 2015: 14 · 2014: 15 · 2013: 11 · 2012: 15
- FWCI
- 5.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (GM0653702, MH064801)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- phosphatidylinositol 3,4,5-trisphosphate, pleckstrin homology domain, phosphatidylinositol 3-kinase, plasma membrane translocation, live-cell imaging, Caenorhabditis elegans, Drosophila, vertebrates
- MeSH terms
- Algorithms, Amino Acid Sequence, Animals, Humans, Models, Molecular, Models, Theoretical, Molecular Sequence Data, Phylogeny, Protein Binding, Protein Conformation, Recombinant Fusion Proteins, Sequence Alignment, Caenorhabditis elegans, Phosphatidylinositol Phosphates, Microscopy, Confocal, Phosphatidylinositol 4,5-Diphosphate, Phosphatidylinositol 3-Kinases, Proteome, Caenorhabditis elegans Proteins, NIH 3T3 Cells, Mice
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