The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
A role for phosphoinositide 3-kinase in the completion of macropinocytosis and phagocytosis by macrophages
Open accessAbstract
Phosphoinositide 3-kinase (PI 3-kinase) has been implicated in growth factor signal transduction and vesicular membrane traffic. It is thought to mediate the earliest steps leading from ligation of cell surface receptors to increased cell surface ruffling. We show here that inhibitors of PI 3-kinase inhibit endocytosis in macrophages, not by interfering with the initiation of the process but rather by preventing its completion. Consistent with earlier studies, the inhibitors wortmannin and LY294002 inhibited fluid-phase pinocytosis and Fc receptor-mediated phagocytosis, but they had little effect on the receptor-mediated endocytosis of diI-labeled, acetylated, low density lipoprotein. Large solute probes of endocytosis reported greater inhibition by wortmannin than smaller probes did, indicating that macropinocytosis was affected more than micropinocytosis. Since macropinocytosis and phagocytosis are actin-mediated processes, we expected that their inhibition by wortmannin resulted from deficient signaling from macrophage colony-stimulating factor (M-CSF) receptors or Fc receptors to the actin cytoskeleton. However, video microscopy showed cell surface ruffling in wortmannin-treated cells, and increased ruffling after addition of M-CSF or phorbol myristate acetate. Quantitative measurements of video data reported slightly diminished ruffling in wortmannin-treated cells. Remarkably, the ruffles that formed in wortmannin-treated macrophages all receded into the cytoplasm without closing into macropinosomes. Similarly, wortmannin and LY294002 did not inhibit the extension of actin-rich pseudopodia along IgG-opsonized sheep erythrocytes, but instead prevented them from closing into phagosomes. These findings indicate that PI 3-kinase is not necessary for receptor-mediated stimulation of pseudopod extension, but rather functions in the closure of macropinosomes and phagosomes into intracellular organelles.
Overview
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
Verification
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Hence, consumption of 4,5-PIP2 by PI3K must contribute to the dissociation of PLCδ-PH-GFP.”
From Localized Biphasic Changes in Phosphatidylinositol-4,5-Bisphosphate at Sites of Phagocytosis (2000) · cites this paper as Araki et al. 1996
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“This kinase appears to be essential for phagocytosis since inhibitors such as wortmannin impair particle engulfment (Ninomiya et al. 1994; Araki et al. 1996; Cox et al. 1999).”
From Localized Biphasic Changes in Phosphatidylinositol-4,5-Bisphosphate at Sites of Phagocytosis (2000) · cites this paper as Araki et al. 1996
The cited source says what the claim attributes to it.
In the citing paper
“The increase in 3,4,5-PIP3 predicted to occur during phagocytosis, based on the reported activation of PI3K (Araki et al. 1996; Cox et al. 1999), did not affect the distribution of PLCδ-PH-GFP.”
From Localized Biphasic Changes in Phosphatidylinositol-4,5-Bisphosphate at Sites of Phagocytosis (2000) · cites this paper as Araki et al. 1996
The cited source says what the claim attributes to it.
In the citing paper
“While wortmannin-treated cells fail to internalize particles, they nevertheless display marked actin reassembly under the adherent RBCs (Araki et al. 1996; Cox et al. 1999; and our own observations, not shown).”
From Localized Biphasic Changes in Phosphatidylinositol-4,5-Bisphosphate at Sites of Phagocytosis (2000) · cites this paper as Araki et al. 1996
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Vlahos, C. J., Matter, W. F., Hui, K. Y., & Brown, R. F. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)37680-9 · Cited by 3,248 · cited 3×
“Its inhibitory effects are reversible, and it is specific for PI 3-kinase (35).”
BackgroundResultOncogenes and signal transduction
Cantley, L. C., Auger, K. R., Carpenter, C. F., Duckworth, B. C., Graziani, A., Kapeller, R., & Soltoff, S. P. (1991) · Cell · doi:10.1016/0092-8674(91)90639-g · Cited by 2,697 · cited 1×
“Nonetheless, a number of cellular processes require PI 3-kinase activity, including mitogenesis (6), membrane ruffling (18, 36), fluid-phase pinocytosis (3, 8), the respiratory burst (2, 22), and lysosomal enzyme sorting (5, 10, 25).”
BackgroundGoldstein, J. L., Ho, Y. K., Basu, S. K., & Brown, M. S. (1979) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.76.1.333 · Cited by 2,447 · cited 1×
“To confirm that the observed uptake of diI-acLDL was receptor mediated, labeling and endocytosis of diI-acLDL were measured in the presence and absence of excess mBSA, which competitively binds the scavenger receptor (13, 17).”
BackgroundArcaro, A., & Wymann, M. P. (1993) · Biochemical Journal · doi:10.1042/bj2960297 · Cited by 1,138 · cited 1×
“Wortmannin inhibits agonist-induced responses but not phorbol ester-induced responses in neutrophils (1, 2), indicating that PI 3-kinase functions upstream of protein kinase C in that signaling cascade.”
BackgroundType I macrophage scavenger receptor contains α-helical and collagen-like coiled coils
Kodama, T., Freeman, M. W., Rohrer, L., Zabrecky, J. R., Matsudaira, P. T., & Krieger, M. (1990) · Nature · doi:10.1038/343531a0 · Cited by 1,036
Phosphatidylinositol 3-Kinase Encoded by Yeast VPS 34 Gene Essential for Protein Sorting
Schu, P. V., Takegawa, K., Fry, M. J., Stack, J. H., Waterfield, M. D., & Emr, S. D. (1993) · Science · doi:10.1126/science.8385367 · Cited by 778 · cited 1×
“Nonetheless, a number of cellular processes require PI 3-kinase activity, including mitogenesis (6), membrane ruffling (18, 36), fluid-phase pinocytosis (3, 8), the respiratory burst (2, 22), and lysosomal enzyme sorting (5, 10, 25).”
BackgroundSwanson, J. A., & Watts, C. K. W. (1995) · Trends in Cell Biology · doi:10.1016/s0962-8924(00)89101-1 · Cited by 771
Self-citationYano, H., Nakanishi, S., Kimura, K. D., Hanai, N., Saitoh, Y., Fukui, Y., Nonomura, Y., & Matsuda, Y. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)74466-4 · Cited by 725
Phosphoinositides as Regulators in Membrane Traffic
Camilli, P. V. D., Emr, S. D., McPherson, P. S., & Novick, P. (1996) · Science · doi:10.1126/science.271.5255.1533 · Cited by 706 · cited 1×
“It phosphorylates phosphoinositides at the D3 hydroxyl of inositol, producing phosphatidylinositol 3-phosphate, phosphatidylinositol (3, 4)-bisphosphate, or phosphatidylinositol (3, 4, 5)-trisphosphate (11).”
BackgroundMutations in human dynamin block an intermediate stage in coated vesicle formation
van der Bliek, A., Redelmeier, T., Damke, H., Tisdale, E. J., Meyerowitz, E. M., & Schmid, S. (1993) · The Journal of Cell Biology · doi:10.1083/jcb.122.3.553 · Cited by 698 · cited 1×
“tein implicated in elathrin-mediated endocytosis (14, 34).”
Cited by
Sorted by citations
Items 301–400 of 947
Egami, Y., Fukuda, M., & Araki, N. (2011) · Journal of Cell Science · doi:10.1242/jcs.083881 · Cited by 89
“Critical-point-dried specimens were coated with an osmium plasma coater and observed by a field emission scanning electron microscope (Hitachi S900), as previously described (Araki et al., 1996).”
BackgroundMethodInfluentialSelf-citationSelective Inhibition of IgG-Mediated Phagocytosis in Gelsolin-Deficient Murine Neutrophils
Serrander, L., Skarman, P., Rasmussen, B., Witke, W., Lew, D. P., Krause, K., Stendahl, O. I., & Nüße, O. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.5.2451 · Cited by 84
SHP-1 regulates Fcγ receptor–mediated phagocytosis and the activation of RAC
Kant, A. M., De, P., Peng, X., Yi, T., Rawlings, D. J., Kim, J. S., & Durden, D. L. (2002) · Blood · doi:10.1182/blood.v100.5.1852.h81702001852_1852_1859 · Cited by 81
Seastone, D. J., Zhang, L., Buczynski, G., Rebstein, P., Weeks, G., Spiegelman, G., & Cardelli, J. (1999) · Molecular Biology of the Cell · doi:10.1091/mbc.10.2.393 · Cited by 97
“For instance, PKC, PI 3-kinases, and protein tyrosine kinases (PTK) have been implicated in regulating the internalization of particles in macrophages and neutrophils (Allen and Aderem, 1995; Hutchinson et al., 1995; Araki et al., 1996).”
BackgroundCritical role for PI3-kinase in regulating the use of proteins as an amino acid source
Palm, W., Araki, J., King, B., Dematteo, R. G., & Thompson, C. B. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1712726114 · Cited by 80
“Besides Ras, PI3-kinase is an important regulator of macropinosome formation, and pharmacological inhibition of PI3-kinase suppresses macropinocytosis (11, 17).”
BackgroundDoodnauth, S. A., Grinstein, S., & Maxson, M. E. (2018) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2018.0147 · Cited by 78
Endocytosis and intracellular transport of ricin: recent discoveries
Sandvig, K., & van Deurs, B. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)00529-3 · Cited by 82
Tsunetsugu‐Yokota, Y., Morikawa, Y., Isogai, M., Kawana‐Tachikawa, A., Odawara, T., Nakamura, T., Grassi, M. F. R., Autran, B., & Iwamoto, A. (2003) · Journal of Virology · doi:10.1128/jvi.77.19.10250-10259.2003 · Cited by 82
“The phosphatidylinositol 3-kinase inhibitor LY294002 inhibits signal transduction essential in membrane ruffling (4) and was used as an inhibitor of macropinocytosis.”
MethodTwo‐dimensional maps and databases of the human macrophage proteome and secretome
Dupont, A., Tokarski, C., Dekeyzer, O., Guihot, A., Amouyel, P., Rolando, C. H., & Pinet, F. (2004) · PROTEOMICS · doi:10.1002/pmic.200300691 · Cited by 82
Vertebrate Epidermal Cells Are Broad-Specificity Phagocytes That Clear Sensory Axon Debris
Rasmussen, J. P., Sack, G. S., Martin, S. M., & Sagasti, A. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.3613-14.2015 · Cited by 82
“For example, inhibition of PI3K (phosphatidylinositol 3-kinase) only affects phagocytosis of beads at least 3 m in diameter (Araki et al., 1996; Cox et al., 1999).”
BackgroundAmphiphilic carbon dots as versatile vectors for nucleic acid and drug delivery
Wang, H., He, X., Luo, T., Zhang, J., Liu, Y., & Yu, X. (2017) · Nanoscale · doi:10.1039/c7nr01029j · Cited by 80
PI(3,4)P2 Signaling in Cancer and Metabolism
Gozzelino, L., Santis, M. C. D., Gulluni, F., Hirsch, E., & Martini, M. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.00360 · Cited by 79
“The requirement of PI(3,4,5)P3 in macropinocytosis is demonstrated using PI3K inhibitors (82).”
BackgroundThomann, L., Käuper, P., Rossi, N., Milona, P., Herrmann, B., & McCullough, K. C. (2012) · Journal of Controlled Release · doi:10.1016/j.jconrel.2012.11.015 · Cited by 80
Modulation of phosphoinositide metabolism by pathogenic bacteria
Hilbi, H. (2006) · Cellular Microbiology · doi:10.1111/j.1462-5822.2006.00793.x · Cited by 80
Differential kinase requirements in human and mouse Fc-gamma receptor phagocytosis and endocytosis
Huang, Z.-Y., Barreda, D. R., Worth, R. G., Indik, Z. K., Kim, M.-K., Chien, P., & Schreiber, A. D. (2006) · Journal of Leukocyte Biology · doi:10.1189/jlb.0106019 · Cited by 80
“In contrast, phagocytosis involves assembly of F-actin and is blocked by inhibitors of class I phosphatidyl inositol 3-kinase [22, 23].”
BackgroundFens, M. H. A. M., Mastrobattista, E., de Graaff, A. M., Flesch, F. M., Ultee, A., Rasmussen, J. T., Molema, G., Storm, G., & Schiffelers, R. M. (2008) · Blood · doi:10.1182/blood-2007-06-094763 · Cited by 80
Dynamin‐Actin Cross Talk Contributes to Phagosome Formation and Closure
Marie‐Anaïs, F., Mazzolini, J., Herit, F., & Niedergang, F. (2016) · Traffic · doi:10.1111/tra.12386 · Cited by 78
“The inhibition of FcR-mediated phagocytosis observed when dynamin K44A was expressed is reminiscent of the phenotype obtained with wortmannin, or after interference with the function of ARF6, AP1 or Bcl10, leading to stalled phagocytic cups (6,12,16,22).”
BackgroundHamme, E. V., Dewerchin, H. L., Cornelissen, E., Verhasselt, B., & Nauwynck, H. (2008) · Journal of General Virology · doi:10.1099/vir.0.2008/001602-0 · Cited by 79
“FIPV entry does not occur via phagocytosis nor macropinocytosis Wortmannin and latrunculin B interfere in phagocytosis and macropinocytosis through their action on phos- phatidyl-inositol-3 kinases and actin (Spector et al., 1983; Araki et al., 1996).”
BackgroundHistamine Improves Antigen Uptake and Cross-Presentation by Dendritic Cells
Amaral, M. M., Davio, C. A., Ceballos, A., Salamone, G. V., Cañones, C., Geffner, J. R., & Vermeulen, M. E. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.6.3425 · Cited by 79
Positive Regulation of Phagocytosis by SIRPβ and Its Signaling Mechanism in Macrophages
Hayashi, A., Ohnishi, H., Okazawa, H., Nakazawa, S., Ikeda, H., Motegi, S., Aoki, N., Kimura, S., Mikuni, M., & Matozaki, T. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m400950200 · Cited by 79
Differential Association of Phosphatidylinositol 3-Kinase, SHIP-1, and PTEN with Forming Phagosomes
Kamen, L. A., Levinsohn, J. L., & Swanson, J. A. (2007) · Molecular Biology of the Cell · doi:10.1091/mbc.e07-01-0061 · Cited by 79
“Treatment of macrophages with wortmannin or LY294002, compounds that inhibit the catalytic subunit of PI3K, results in formation of phagocytic cups that are unable to close (Araki et al., 1996; Cox et al., 1999).”
BackgroundSelf-citationLigand Binding Determines Whether CD46 Is Internalized by Clathrin-coated Pits or Macropinocytosis
Crimeen‐Irwin, B., Ellis, S. L., Christiansen, D., Ludford‐Menting, M., Milland, J., Lanteri, M. B., Loveland, B. E., Gerlier, D., & Russell, S. M. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m308261200 · Cited by 79
Song, X., Tanaka, S., Cox, D., & Lee, S. C. (2004) · Journal of Leukocyte Biology · doi:10.1189/jlb.0403128 · Cited by 79
“The requirement for specific signal components in the different stages of phagocytosis has been defined: Particle ingestion via Fc R requires actin assembly, pseudopod extension, and phagosomal closure, and PI-3K has been implicated these processes [9, 10].”
BackgroundFolding graft copolymer with pendant drug segments for co-delivery of anticancer drugs
Tai, W., Mo, R., Lü, Y., Jiang, T., & Gu, Z. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2014.05.004 · Cited by 78
“In contrast, insignificant inhibition on the cellular uptake of nanocarrier was found in the cells pretreated with nystatin (an inhibitor of caveolin-mediated endocytosis) [64] or sodium azide/2-deoxyglucose and wortmannin (inhibitors of macropinocytosis) [65,66].”
Membrane dynamics in phagocytosis
Booth, J. W., Trimble, W. S., & Grinstein, S. (2001) · Seminars in Immunology · doi:10.1006/smim.2001.0332 · Cited by 78
Dendritic cells: New roles for Cdc42 and Rac in antigen uptake?
Nobes, C. D., & Marsh, M. (2000) · Current Biology · doi:10.1016/s0960-9822(00)00736-3 · Cited by 78
Fujioka, Y., Tsuda, M., Hattori, T., Sasaki, J., Sasaki, T., Miyazaki, T., & Ohba, Y. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016324 · Cited by 76
“The treatment of wild-type MEFs with the pan-PI3K inhibitor LY294002 significantly reduced the uptake of dextran, but not that of transferrin (Figure 1A, B), confirming that PI3K is specifically involved in clathrin-independent endocytosis, as reported previously [20].”
ResultPI3K Signaling and Stat92E Converge to Modulate Glial Responsiveness to Axonal Injury
Doherty, J., Sheehan, A. E., Bradshaw, R., Fox, A. N., Lu, T.-Y., & Freeman, M. R. (2014) · PLoS Biology · doi:10.1371/journal.pbio.1001985 · Cited by 77
“PI3K signaling is required for efficient formation of the phagocytic cup in macrophages [61,64,65], and loss of PI3K has been reported to lead to a delay in clearance of cell corpses and myelin [62,66,67].”
BackgroundBacterial avoidance of phagocytosis
Celli, J., & Finlay, B. B. (2002) · Trends in Microbiology · doi:10.1016/s0966-842x(02)02343-0 · Cited by 77
Filamentous morphology of bacteria delays the timing of phagosome morphogenesis in macrophages
Prashar, A., Bhatia, S., Gigliozzi, D., Martin, T., Duncan, C., Guyard, C., & Terebiznik, M. R. (2013) · Journal of Cell Biology · doi:10.1083/jcb.201304095 · Cited by 76
“1 D; Araki et al., 1996, 2003; Cox et al., 1999).”
Kannan, S., Audet, A., Huang, H., Chen, L.-J., & Wu, M. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.4.2396 · Cited by 80
“This pathway has been shown to modulate many cytoskeleton-based cellular processes, including adhesion, cell spreading, macropinocytosis, and phagocytosis (14).”
BackgroundDewitt, S., Tian, W., & Hallett, M. B. (2006) · Journal of Cell Science · doi:10.1242/jcs.02756 · Cited by 76
“This latter finding has also been reported in macrophages, where treatment with LY294002 also arrested phagosome formation before closure, but after phagocytic cup formation (Cox et al., 1999; Araki et al., 1996).”
ResultAmphiphilic glycopolymer nanoparticles as vehicles for nasal delivery of peptides and proteins
Zheng, C., Guo, Q., Wu, Z., Sun, L., Zhang, Z., Li, C., & Zhang, X. (2013) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2013.04.027 · Cited by 76
“Wortmannin is a phosphatidyl inositol-3-phosphate inhibitor (Araki et al., 1996), while amiloride can inhibits Na/H ion exchange in plasma membrane (Hewlett et al.”
Amphiphysin IIm, a Novel Amphiphysin II Isoform, Is Required for Macrophage Phagocytosis
Gold, E. S., Morrissette, N. S., Underhill, D. M., Guo, J., Bassetti, M. F., & Aderem, A. A. (2000) · Immunity · doi:10.1016/s1074-7613(00)80181-8 · Cited by 76
“…ofviability and other actin-based processes were unaffected by the expression of the mutant, since RAW- PI3K causes incomplete phagosome closure (Araki et al., 1996; Cox et al., 1999), a phenotype very similar toTT10 cells expressing AmphIImSH32 polymerized actin at the site of particle…”
LRRK2 recruitment, activity, and function in organelles
Bonet‐Ponce, L., & Cookson, M. (2021) · FEBS Journal · doi:10.1111/febs.16099 · Cited by 82
Huang, Y., Lee, H., Tolliver, L. M., & Aronstam, R. S. (2015) · BioMed Research International · doi:10.1155/2015/834079 · Cited by 77
Syndecan 4 Regulates FGFR1 Signaling in Endothelial Cells by Directing Macropinocytosis
Elfenbein, A., Lanahan, A. A., Zhou, T. X., Yamasaki, A., Tkachenko, E., Matsuda, M., & Simons, M. (2012) · Science Signaling · doi:10.1126/scisignal.2002495 · Cited by 81
“To evaluate the contribution of macropinocytosis to FGFR1 uptake, we used labeled neutral 70-kD dextran, a marker for macropinocytosis (31, 32).”
MethodThe Adapter Protein LAT Enhances Fcγ Receptor-mediated Signal Transduction in Myeloid Cells
Tridandapani, S., LYDEN, T. W., Smith, J. L., Carter, J. E., Coggeshall, K. M., & Anderson, C. L. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m909462199 · Cited by 75
Naccache, P. H., Levasseur, S., Lachance, G., Chakravarti, S., Bourgoin, S. G., & McColl, S. R. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m001780200 · Cited by 75
Singh, J., Michel, D. L., Chitanda, J. M., Verrall, R. E., & Badea, I. (2012) · Journal of Nanobiotechnology · doi:10.1186/1477-3155-10-7 · Cited by 74
“Wortmannin, a phosphatidylinositol 3 kinase inhibitor, can be employed to inhibit macropinocytosis [16].”
BackgroundGolebiewska, U. P., Kay, J. G., Masters, T. A., Grinstein, S., Im, W., Pastor, R. W., Scarlata, S., & McLaughlin, S. (2011) · Molecular Biology of the Cell · doi:10.1091/mbc.e11-02-0114 · Cited by 76
“Importance of the fence for phagocytosis Several lines of evidence suggest that local changes in the level of the phosphoinositides PIP2 and PIP3 are important for phagocytosis (Araki et al., 1996; Coppolino et al., 2002; Swanson, 2008).”
BackgroundRupper, A. C., Lee, K., Knecht, D. A., & Cardelli, J. A. (2001) · Molecular Biology of the Cell · doi:10.1091/mbc.12.9.2813 · Cited by 74
“3-kinases in regulating macropinocytosis (Araki et al., 1996),”
BackgroundResultInfluentialA growth factor signaling cascade confined to circular ruffles in macrophages
Welliver, T. P., & Swanson, J. A. (2012) · Biology Open · doi:10.1242/bio.20121784 · Cited by 75
“The PI3K inhibitors wortmannin and LY294002 do not inhibit ruffling or phagocytic cup formation, but instead inhibit contractile activities that close phagosomes and macropinosomes into the cell (Amyere et al., 2000; Araki et al., 1996; Swanson et al., 1999).”
BackgroundSelf-citationHu, W. S., Qiu, L., Cheng, L., Hu, Q., Liu, Y., Hu, Z., Chen, D., & Cheng, L. (2016) · Acta Biomaterialia · doi:10.1016/j.actbio.2016.03.027 · Cited by 73
Lo, Y., Sung, K.-H., Chiu, C., & Wang, L. (2013) · Molecular Pharmaceutics · doi:10.1021/mp300432s · Cited by 74
Cellular uptake pathways of lipid-modified cationic polymers in gene delivery to primary cells
Hsu, C. Y. M., & Uludağ, H. (2012) · Biomaterials · doi:10.1016/j.biomaterials.2012.06.093 · Cited by 72
“Wortmannin Inhibitor of phosphatidyl inositol-3-phosphate (PI3K) Macro-pinocytosis 75 nM [62]”
Association of early endosomal autoantigen 1 with macropinocytosis in EGF‐stimulated a431 cells
HAMASAKI, M., Araki, N., & Hatae, T. (2004) · The Anatomical Record Part A Discoveries in Molecular Cellular and Evolutionary Biology · doi:10.1002/ar.a.20027 · Cited by 71
Self-citationP2Y4 Receptor-Mediated Pinocytosis Contributes to Amyloid Beta-Induced Self-Uptake by Microglia
Li, H.-Q., Chen, C., Dou, Y., Wu, H.-J., Liu, Y.-J., Lou, H.-F., Zhang, J.-M., Li, X.-M., Wang, H., & Duan, S. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.00544-13 · Cited by 73
“Activation of PI3K at the plasma membrane has been found to be related to the growth factor-induced cytoskeletal remodeling and membrane ruffling that leads to increased pinocytosis (17, 38).”
BackgroundMethodIwata, T., Hirose, H., Sakamoto, K., Hirai, Y., Arafiles, J. V. V., Akishiba, M., Imanishi, M., & Futaki, S. (2021) · Angewandte Chemie International Edition · doi:10.1002/anie.202105527 · Cited by 71
Effects of the nanostructure of dendrimer/DNA complexes on their endocytosis and gene expression
Peng, S., Su, C., Wei, M.-C., Chen, C., Liao, Z.-X., Lee, P.-W., Chen, H., & Sung, H. (2010) · Biomaterials · doi:10.1016/j.biomaterials.2010.03.059 · Cited by 70
Invasion and persistence of Mycoplasma bovis in embryonic calf turbinate cells
Bürki, S., Gaschen, V., Stoffel, M. H., Stojiljković, A., Joachim Frey, A., Kuehni-Boghenbor, K., & Pilo, P. (2015) · Veterinary Research · doi:10.1186/s13567-015-0194-z · Cited by 70
“These chemicals inhibit macropinocytosis and phagocytosis [45], although”
BackgroundRoma‐Rodrigues, C., Raposo, L. R., Cabral, R. M., Paradinha, F., Baptista, P. V., & Fernandes, A. R. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18010162 · Cited by 72
“Clathrin-mediated endocytosis Dynamin 2 Gene knockdown [183,184]”
BackgroundGanesan, L. P., Guo, W., Pengal, R. A., Moldovan, L., Moldovan, N. I., Ostrowski, M. C., & Tridandapani, S. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m408188200 · Cited by 69
Dynamin Regulates Focal Exocytosis in Phagocytosing Macrophages
Di, A., Nelson, D. J., Bindokas, V. P., Brown, M. E., Libunao, F., & Palfrey, H. C. (2003) · Molecular Biology of the Cell · doi:10.1091/mbc.e02-09-0626 · Cited by 69
At the Crossroads of Chemistry and Cell Biology: Inhibiting Membrane Traffic by Small Molecules
von Kleist, L., & Haucke, V. (2011) · Traffic · doi:10.1111/j.1600-0854.2011.01292.x · Cited by 72
Sarantis, H., & Gray‐Owen, S. D. (2007) · Cellular Microbiology · doi:10.1111/j.1462-5822.2007.00947.x · Cited by 67
“This is a logical result, as both Syk and PI3K play a role in phagosomal closure during phagocytosis, shown by the strikingly comparable phagocytic defects (an apparent inability to enclose the bound particle into a phagosome because of insufficient pseudopod extension) in both PI3K-inhibited (Araki et al., 1996; Cox…”
BackgroundDiffusion Barriers, Mechanical Forces, and the Biophysics of Phagocytosis
Ostrowski, P. P., Grinstein, S., & Freeman, S. A. (2016) · Developmental Cell · doi:10.1016/j.devcel.2016.06.023 · Cited by 75
“Thus, engulfment of large particles (R3 mm) requires activation of PI3K, but this step is dispensable in the case of smaller ones (Araki et al., 1996; Cox et al., 1999).”
BackgroundYang, J., Tu, J., Lamers, G. E. M., Olsthoorn, R. C. L., & Kros, A. (2017) · Advanced Healthcare Materials · doi:10.1002/adhm.201700759 · Cited by 69
Procyk, K. J., Kovarik, P., von Gabain, A., & Baccarini, M. (1999) · Infection and Immunity · doi:10.1128/iai.67.3.1011-1017.1999 · Cited by 69
“PI 3-K (3) and PLD (27) have been implicated in the process of phagocytosis.”
Role of microtubules and myosins in Fc gamma receptor-mediated phagocytosis
Araki, N. (2006) · Frontiers in bioscience · doi:10.2741/1897 · Cited by 64
Self-citationWang, J. T. H., Kerr, M. C., Karunaratne, S. M., Jeanes, A., Yap, A. S., & Teasdale, R. D. (2010) · PLoS ONE · doi:10.1371/journal.pone.0013763 · Cited by 67
“PI(3)K activity has also been shown to be required for macropinosome formation [10,28], implicating the direct role of its phosphorylation targets, 3-phosphoinositides, in the process.”
BackgroundFcγ Receptor Signaling in Phagocytes
Joshi, T., Butchar, J. P., & Tridandapani, S. (2006) · International Journal of Hematology · doi:10.1532/ijh97.06140 · Cited by 66
“Interestingly, inhibition of PI3-kinase with wortmannin or LY294002 also did not inhibit phagocytic cup formation; however, closure of the phagosomes around the particles was blocked [ 26 ].”
BackgroundEffect of 3-methyladenine on the Fusion Process of Macropinosomes in EGF-stimulated A431 Cells
Araki, N., Hamasaki, M., Egami, Y., & Hatae, T. (2006) · Cell Structure and Function · doi:10.1247/csf.06029 · Cited by 65
“…of macropinosomes from cell surface ruffles is highly dependent on the actin cytoskeleton reorganization which is spatiotemporally coordinated by the Rho family GTPases and phosphoinositide signaling (Anton et al., 2003; Araki et al., 2003; Araki et al., 2000; Araki et al., 1996; Maniak, 2001).”
BackgroundMethodInfluentialSelf-citationp85α subunit of class IA PI-3 kinase is crucial for macrophage growth and migration
Munugalavadla, V., Borneo, J., Ingram, D. A., & Kapur, R. (2005) · Blood · doi:10.1182/blood-2004-10-4041 · Cited by 67
Jang, S., Ohtani, K., Fukuoh, A., Yoshizaki, T., Fukuda, M., Motomura, W., Mori, K., Fukuzawa, J., Kitamoto, N., Yoshida, I., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m807477200 · Cited by 65
A C2 domain protein kinase initiates phagocytosis in the protozoan parasite Entamoeba histolytica
Somlata, S., Bhattacharya, S., & Bhattacharya, A. (2011) · Nature Communications · doi:10.1038/ncomms1199 · Cited by 64
“In the presence of PI3K inhibitors, incomplete phagosomes appear as actin-rich phagocytic cups, suggesting that PI3K may be involved in organizing the later stages of phagocytosi”
BackgroundClathrin‐independent internalization and recycling
Gong, Q., Huntsman, C., & Ma, D. (2007) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2007.00148.x · Cited by 63
“wortmannin) [72], without disrupting clathrin-dependent internalization.”
Mechanism of Lentinan Intestinal Absorption: Clathrin-Mediated Endocytosis and Macropinocytosis
Zheng, Z., Pan, X., Wang, H., Wu, Z.-J., Sullivan, M. A., Liu, Y., Liu, J., Wang, K., & Zhang, Y. (2021) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.1c00349 · Cited by 65
SHIP-1 Increases Early Oxidative Burst and Regulates Phagosome Maturation in Macrophages
Kamen, L. A., Levinsohn, J. L., Cadwallader, A. M., Tridandapani, S., & Swanson, J. A. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.11.7497 · Cited by 63
“3 -Phosphoinositides (3 -PIs)(3) generated early during phagocytosis regulate closure of the phagocytic cup (2).”
BackgroundSelf-citationUptake and trafficking of DNA in keratinocytes: evidence for DNA-binding proteins
Basner‐Tschakarjan, E., Mirmohammadsadegh, A., Baer, A., & Hengge, U. R. (2004) · Gene Therapy · doi:10.1038/sj.gt.3302221 · Cited by 63
García-García, E., Rosales, R., & Rosales, C. (2002) · Journal of Leukocyte Biology · doi:10.1189/jlb.72.1.107 · Cited by 63
“However, macrophages also seem to require PI 3-K and ERK for phagocytosis [14, 15].”
BackgroundCanetti, C. D. A., Hu, B., Curtis, J. L., & Peters-Golden, M. L. (2003) · Blood · doi:10.1182/blood-2003-02-0534 · Cited by 62
Jayachandran, R., Gatfield, J., Massner, J., Albrecht, I., Zanolari, B., & Pieters, J. (2007) · Molecular Biology of the Cell · doi:10.1091/mbc.e07-07-0640 · Cited by 62
“Fluid phase uptake including macropinocytosis ensures the internalization of nonparticulate material in an actin-dependent process (Maniak et al., 1995; Steinman and Swanson, 1995; Araki et al., 1996; Amyere et al., 2000; Johannes and Lamaze, 2002).”
Hyaluronic acid-based carbon dots for efficient gene delivery and cell imaging
Wang, H., Zhang, J., Liu, Y., Luo, T., He, X., & Yu, X. (2017) · RSC Advances · doi:10.1039/c7ra01417a · Cited by 62
Leveraging Siglec-8 endocytic mechanisms to kill human eosinophils and malignant mast cells
O’Sullivan, J. A., Carroll, D. J., Cao, Y., Salicru, A. N., & Bochner, B. S. (2017) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2017.06.028 · Cited by 63
Sarantis, H., Balkin, D. M., Camilli, P. V. D., Isberg, R. R., Brumell, J. H., & Grinstein, S. (2012) · Cell Host & Microbe · doi:10.1016/j.chom.2012.01.010 · Cited by 63
“Activation of class I phosphatidylinositol 3-kinase (PI3K) is essential for optimal Fcg receptor, Dectin-1, and complement receptor-mediated phagocytosis by professional phagocytes (Araki et al., 1996; Cox et al., 1999; Herre et al., 2004).”
BackgroundCharacterization of glyceraldehyde-3-phosphate dehydrogenase as a novel transferrin receptor
Kumar, S., Sheokand, N., Mhadeshwar, M. A., Raje, C. I., & Raje, M. (2011) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2011.10.016 · Cited by 62
Basquin, C., Malardé, V., Mellor, P., Anderson, D. H., Meas‐Yedid, V., Olivo‐Marín, J., Dautry‐Varsat, A., & Sauvonnet, N. (2013) · Journal of Cell Science · doi:10.1242/jcs.110932 · Cited by 69
Cole, L., Hyde, G. J., & Ashford, A. E. (1997) · PROTOPLASMA · doi:10.1007/bf02539802 · Cited by 61
Krysko, D. V., Brouckaert, G., Kalai, M., Vandenabeele, P., & D'Herde, K. G. M. A. (2003) · Journal of Morphology · doi:10.1002/jmor.10161 · Cited by 61
“E-mail: dmitri.krysko@UGent.be DOI: 10.1002/jmor.10161 © 2003 WILEY-LISS, INC. Figure 1 son and Watts, 1995; Akari et al., 1996; Jones and Willingham, 1999; Somersan and Bhardwaj, 2001; Toril et al., 2001).”
InfluentialInhibitory ITAMs: a matter of life and death
da Silva, F. P., Aloulou, M., Benhamou, M., & Monteiro, R. C. (2008) · Trends in Immunology · doi:10.1016/j.it.2008.05.001 · Cited by 60
Alfatama, M., Lim, L. Y., & Wong, T. W. (2018) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.8b00391 · Cited by 60
Phosphatidylinositol-3 kinase is involved in ruffled border formation in osteoclasts
Nakamura, I., Sasaki, T., Tanaka, S., Takahashi, N., Jimi, E., Kurokawa, T., Kita, Y., Ihara, S., Suda, T., & Fukui, Y. (1997) · Journal of Cellular Physiology · doi:10.1002/(sici)1097-4652(199708)172:2 · Cited by 61
Zhang, W.-Y., Gaynor, P. M., & Kruth, H. S. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.50.31700 · Cited by 60
Booth, J. W., Telio, D., Liao, E. H., McCaw, S. E., Matsuo, T., Grinstein, S., & Gray‐Owen, S. D. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m211879200 · Cited by 60
Rho Family Proteins and Regulation of the Actin Cytoskeleton
Ridley, A. J. (1999) · Progress in molecular and subcellular biology · doi:10.1007/978-3-642-58591-3_1 · Cited by 60
Patel, D., Rorbach, J., Downes, K., Szukszto, M. J., Pękalski, M. Ł., & Minczuk, M. A. (2017) · Scientific Reports · doi:10.1038/s41598-017-13227-0 · Cited by 62
Eom, H.-J., & Choi, J. (2019) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2019.108774 · Cited by 59
García-García, E., Sánchez‐Mejorada, G., & Rosales, C. (2001) · PubMed · Cited by 59
Redka, D. S., Gütschow, M., Grinstein, S., & Canton, J. (2018) · Molecular Biology of the Cell · doi:10.1091/mbc.e17-06-0419 · Cited by 58
“Both induced and constitutive forms of macropinocytosis are known to be PtdIns3Kand actin-dependent (Araki et al., 1996; Zhou et al., 1998; Amyere et al., 2000; Hoeller et al., 2013).”
BackgroundThe pervasiveness of macropinocytosis in oncological malignancies
Commisso, C. (2018) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2018.0153 · Cited by 57
Using macropinocytosis for intracellular delivery of therapeutic nucleic acids to tumour cells
Desai, A. S., Hunter, M. R., & Kapustin, A. N. (2018) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2018.0156 · Cited by 58
Cooney, D. S., Phee, H., Jacob, A., & Coggeshall, K. M. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.2.844 · Cited by 58
β1 and β2 integrins activate different signalling pathways in monocytes
REYES-REYES, M., Mora, N., González, G. R., & Rosales, C. (2002) · Biochemical Journal · doi:10.1042/0264-6021:3630273 · Cited by 58
Collins, R. F., Touret, N., Kuwata, H., Tandon, N. N., Grinstein, S., & Trimble, W. S. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.045104 · Cited by 57
Combinatorial Targeting of the Macropinocytotic Pathway in Leukemia and Lymphoma Cells
Nishimura, S., Takahashi, S., Kamikatahira, H., Kuroki, Y., Jaalouk, D. E., O'Brien, S. M., Koivunen, E., Arap, W., Pasqualini, R., Nakayama, H., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m708849200 · Cited by 57
Khandani, A., Eng, E. W. Y., Jongstra‐Bilen, J., Schreiber, A. D., Douda, D. N., Samavarchi‐Tehrani, P., & Harrison, R. E. (2007) · Journal of Leukocyte Biology · doi:10.1189/jlb.0706469 · Cited by 57
“MT depolymerization effects on particle internalization are a function of particle size PI-3K has been implicated in pseudopod extension and closure [ 50 ].”
cRGDyK modified pH responsive nanoparticles for specific intracellular delivery of doxorubicin
Qiu, L., Hu, Q. C., Cheng, L., Li, L., Tian, C., Chen, W., Chen, Q., Hu, W. S., Xu, L., Yang, J. P., et al. (2015) · Acta Biomaterialia · doi:10.1016/j.actbio.2015.11.037 · Cited by 57
SH2-B Is Required for Growth Hormone-induced Actin Reorganization
Herrington, J. B., Diakonova, M., Rui, L., Gunter, D. R., & Carter‐Su, C. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.17.13126 · Cited by 57
Yap/Taz promote the scavenging of extracellular nutrients through macropinocytosisPreprint
King, B., Araki, J., Palm, W., & Thompson, C. B. (2020) · Genes & Development · doi:10.1101/gad.340661.120 · Cited by 56
“Evolutionarily conserved role for Gas6/Axl/PI3K signaling in the activation of macropinocytosis.”
BackgroundInfluential
Metadata
- Authors
- Araki, N., Johnson, M. T., & Swanson, J. A.
- Affiliations
- Harvard University (US)
- ORCID
- Venue
- The Journal of cell biology
- Publisher
- Rockefeller University Press
- Published
- 1996-12-01
- Volume
- 135
- Issue
- 5
- Pages
- 1249-1260
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2121091
- OpenAlex
- W2104603012
- Cited by
- 949
- References
- 39
- Citations by year
- 2026: 9 · 2025: 22 · 2024: 25 · 2023: 17 · 2022: 28 · 2021: 37 · 2020: 38 · 2019: 20 · 2018: 39 · 2017: 35 · 2016: 51 · 2015: 26 · 2014: 49 · 2013: 46 · 2012: 48
- FWCI
- 8.02
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- phosphatidylinositol 3-kinase, macropinocytosis, phagocytosis, macrophages, wortmannin, LY294002, actin cytoskeleton, Fc receptors, macrophage colony-stimulating factor, pseudopod extension, micropinocytosis
- MeSH terms
- Wortmannin, Androstadienes, Animals, Cell Membrane, Cells, Cultured, Chromones, Enzyme Inhibitors, Female, Fluorescent Dyes, Lysosomes, Macrophages, Male, Mice, Inbred C3H, Morpholines, Phagocytosis, Phagosomes, Pinocytosis, Pseudopodia, Receptors, Fc, Tetradecanoylphorbol Acetate, Organelles, Macrophage Colony-Stimulating Factor, Phosphotransferases (Alcohol Group Acceptor), Phosphatidylinositol 3-Kinases, 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
