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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.
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“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
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“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
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“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
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“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
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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).”
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Differential signaling during macropinocytosis in response to M-CSF and PMA in macrophages
Yoshida, S., Gaeta, I., Pacitto, R., Krienke, L. K., Alge, O., Gregorka, B., & Swanson, J. A. (2015) · Frontiers in Physiology · doi:10.3389/fphys.2015.00008 · Cited by 60
“Earlier studies showed that PMA-stimulated macropinocytosis could be inhibited by the PI3K inhibitors LY294002 and wortmannin, which indicated that PI3K functions downstream of PLCγ1 and DAG (Araki et al., 1996).”
BackgroundSelf-citationCummings, H., Barbi, J. J., Reville, P. K., Oghumu, S., Zorko, N. A., Sarkar, A., Keiser, T. L., Lu, B., Rückle, T., Varikuti, S., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1110339109 · Cited by 56
Hazeki, K., Kinoshita, S., Matsumura, T., Nigorikawa, K., Kubo, H., & Hazeki, O. (2006) · Molecular Pharmacology · doi:10.1124/mol.105.021162 · Cited by 56
“PI3K is indispensable for these processes regardless of the target particle (Ninomiya et al., 1994; Araki et al., 1996; Sun et al., 2003).”
BackgroundKruth, H. S. (2013) · Current Pharmaceutical Design · doi:10.2174/1381612811319330005 · Cited by 54
“LY294002 and wortmannin, two inhibitors of all PI3K isoforms, inhibit macropinocytosis in M-CSF differentiated bone marrow-derived mouse macrophages as assessed by phasecontrast microscopy [24, 47].”
BackgroundPhosphoinositide Lipids and the Legionella Pathogen Vacuole
Haneburger, I., & Hilbi, H. (2013) · Current topics in microbiology and immunology · doi:10.1007/82_2013_341 · Cited by 56
“PtdIns(3,4,5)P3 is produced by type I PI3Ks which can be inhibited by the structurally unrelated inhibitors, wortmannin or LY294002 (Araki et al. 1996; Cox et al. 1999).”
BackgroundC-Reactive Protein Induces Signaling Through FcγRIIa on HL-60 Granulocytes,
Chi, M., Tridandapani, S., Zhong, W., Coggeshall, K. M., & Mortensen, R. F. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.3.1413 · Cited by 55
Coppolino, M. G., Chen, K., Mohtashami, M., Schreiber, A. D., Brumell, J. H., Finlay, B. B., Grinstein, S., & Trimble, W. S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m007792200 · Cited by 55
pH-triggered degradable polymeric micelles for targeted anti-tumor drug delivery
Qiu, L., Zhu, M., Gong, K., Peng, H., Ge, L., Zhao, L., & Chen, J. (2017) · Materials Science and Engineering C · doi:10.1016/j.msec.2017.04.137 · Cited by 54
Alnouri, M. W., Roquid, K. A., Bonnavion, R., Cho, H., Heering, J., Kwon, J., Jäger, Y., Wang, S., Günther, S., Wettschureck, N., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2407130121 · Cited by 59
Chiu, Y., Chen, S., Chen, J., Chen, K., Chen, H., & Sung, H. (2010) · ACS Nano · doi:10.1021/nn102644u · Cited by 54
The tyrosine kinase Syk promotes phagocytosis of Francisella through the activation of Erk
Parsa, K. V. L., Butchar, J. P., Rajaram, M. V. S., Cremer, T. J., & Tridandapani, S. (2008) · Molecular Immunology · doi:10.1016/j.molimm.2008.01.011 · Cited by 54
Hagiwara, K., Nakata, M., Koyama, Y., & Sato, T. (2012) · Biomaterials · doi:10.1016/j.biomaterials.2012.06.040 · Cited by 55
Phosphatidylinositol 3-kinase and ERK are required for NF-κB activation but not for phagocytosis
García-García, E., Sánchez‐Mejorada, G., & Rosales, C. (2001) · Journal of Leukocyte Biology · doi:10.1189/jlb.70.4.649 · Cited by 64
Phagocytosis: what’s on the menu?
Lancaster, C. E., Ho, C. Y., Hipolito, V. E. B., Botelho, R. J., & Terebiznik, M. R. (2019) · Biochemistry and Cell Biology · doi:10.1139/bcb-2018-0008 · Cited by 49
A Heparan Sulfate‐Facilitated and Raft‐Dependent Macropinocytosis of Eosinophil Cationic Protein
Fan, T.-C., Chang, H., Chen, I., Wang, H. P., & Chang, M. D. (2007) · Traffic · doi:10.1111/j.1600-0854.2007.00650.x · Cited by 53
“Furthermore, PI3K is necessary for macropinosome closure (43), and the quercetin derivative LY294002 is known to inhibit PI3K and block maintenance, maturation Figure 4: Cell growth is inhibited following ECP internalization.”
BackgroundRuffles limit diffusion in the plasma membrane during macropinosome formation
Welliver, T. P., Chang, S. L., Linderman, J. J., & Swanson, J. A. (2011) · Journal of Cell Science · doi:10.1242/jcs.091538 · Cited by 51
“Previous studies identified molecules that regulate macropinocytosis, including phosphoinositide 3-kinase (PI3K) and Rac1 (Araki et al., 1996; Yoshida et al., 2009).”
Self-citationLee, C.-H., Kasala, D., Na, Y., Lee, M. S., Kim, S. W., Jeong, J. H., & Yun, C. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2014.03.060 · Cited by 52
“This sort of pathway is not sizespecific and can internalize small or large particles [47].”
BackgroundSingle Virus Tracking with Quantum Dots Packaged into Enveloped Viruses Using CRISPR
Yang, Y., Tang, Y.-D., Hu, Y. H., Yu, F., Xiong, J., Sun, M., Lyu, C., Peng, J., Tian, Z., Cai, X., et al. (2020) · Nano Letters · doi:10.1021/acs.nanolett.9b05103 · Cited by 52
Arafiles, J. V. V., Hirose, H., Akishiba, M., Tsuji, S., Imanishi, M., & Futaki, S. (2020) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.0c00064 · Cited by 55
Quinn, S. E., Huang, L., Kerkvliet, J. G., Swanson, J. A., Smith, S., Hoppe, A. D., Anderson, R. B., Thiex, N. W., & Scott, B. L. (2021) · Nature Communications · doi:10.1038/s41467-021-25187-1 · Cited by 50
Self-citationNew insights into the role of the cytoskeleton in phagocytosis of Entamoeba histolytica
Voigt, H., & Guillén, N. (1999) · Cellular Microbiology · doi:10.1046/j.1462-5822.1999.00021.x · Cited by 52
“Inhibition of Syk kinase and PI3-kinase does not inhibit pseudopod extension but does prevent the formation of a closed phagosome (Araki et al., 1996; Crowley et al., 1997).”
BackgroundProtein Kinase C-α Participates in FcγR-Mediated Phagocytosis in Macrophages
Breton, A., & Descoteaux, A. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.3511 · Cited by 52
Ueyama, T., Eto, M., Kami, K., Tatsuno, T., Kobayashi, T., Shirai, Y., Lennartz, M. R., Takeya, R., Sumimoto, H., & Saito, N. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.4.2381 · Cited by 50
Lin, H., Singla, B., Ahn, W., Ghoshal, P., Blahove, M. R., Cherian‐Shaw, M., Chen, A. K., Haller, A. M., Hui, D. Y., Dong, K., et al. (2022) · Science Translational Medicine · doi:10.1126/scitranslmed.add2376 · Cited by 50
“Mechanistically, it was found that growth factors and inflammatory cytokines promote activation of their downstream effectors, Ras and phosphatidylinositol 3-kinase, leading to dynamic phosphorylation of phosphatidylinositols, submembranous actin polymerization, membrane ruffling, macropinosome formation, and macropin…”
BackgroundPedrioli, G., & Paganetti, P. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.595515 · Cited by 50
Francisella Targets Cholesterol-Rich Host Cell Membrane Domains for Entry into Macrophages
Tamilselvam, B., & Daefler, S. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.12.8262 · Cited by 50
“At this concentration it affects late steps of macrophagocytosis and phagocytois, presumably by preventing proper membrane closure and maturation of the phagosome, but has little effect on receptor-mediated endocytosis (27).”
BackgroundAi, J., Maturu, A., Johnson, W., Wang, Y., Marsh, C. B., & Tridandapani, S. (2005) · Blood · doi:10.1182/blood-2005-05-1841 · Cited by 50
Canetti, C. D. A., Serezani, C. H., Atrasz, R. G., White, E. S., Aronoff, D. M., & Peters-Golden, M. L. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.12.8350 · Cited by 50
“SRBCs (ICN Pharmaceuticals) were opsonized with a subagglutinating concentration of IgG rabbit anti-sheep erythrocyte Ab (Cappel Organon Teknika) as previously described (31).”
MethodSyndecan-4 mediates macrophage uptake of group V secretory phospholipase A2-modified LDL
Boyanovsky, B. B., Shridas, P., Simons, M., van der Westhuyzen, D. R., & Webb, N. R. (2008) · Journal of Lipid Research · doi:10.1194/jlr.m800450-jlr200 · Cited by 50
Phosphoinositide Involvement in Phagocytosis and Phagosome Maturation
Botelho, R. J., Scott, C. C., & Grinstein, S. (2004) · Current topics in microbiology and immunology · doi:10.1007/978-3-642-18805-3_1 · Cited by 55
Mechanistic insights into the regulation of circular dorsal ruffle formation
Itoh, T., & Hasegawa, J. (2012) · The Journal of Biochemistry · doi:10.1093/jb/mvs138 · Cited by 49
“Consistenly, PI3K inhibitors such as wortmannin or LY294002 significantly inhibit CDR formation and macropinocytosis (13, 15, 67).”
BackgroundPI3KC2α, a class II PI3K, is required for dynamin-independent internalization pathways
Krag, C., Malmberg, E., & Salcini, A. E. (2010) · Journal of Cell Science · doi:10.1242/jcs.071712 · Cited by 53
“The fact that DT internalization is not prevented by wortmannin (this study) and staurosporine (Skretting et al., 1999), both inhibitors of macropinocytosis (Araki et al., 1996; Dharmawardhane et al., 2000; Mercer and Helenius, 2009; Mercer et al., 2010), suggests that this is probably not the case.”
BackgroundWei, X. P., Li, R., Qiao, S., Chen, X., Xing, G., & Zhang, G. (2020) · Journal of Virology · doi:10.1128/jvi.00709-20 · Cited by 49
Insight into the role of clathrin‐mediated endocytosis inhibitors in SARS‐CoV‐2 infection
Alkafaas, S. S., Abdallah, A. M., Ghosh, S. B., Loutfy, S. A., Elkafas, S. S., Fattah, N. F. A., & Hessien, M. (2022) · Reviews in Medical Virology · doi:10.1002/rmv.2403 · Cited by 53
Shin, O. S., Miller, L. S., Modlin, R. L., Akira, S., Uematsu, S., & Hu, L. T. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0900724 · Cited by 49
“PI3K is a major regulator for phagocytosis of large particles (28).”
BackgroundZenni, M. K., Giardina, P. C., Harvey, H. A., Shao, J., Ketterer, M. R., Lubaroff, D. M., Williams, R. D., & Apicella, M. A. (2000) · Infection and Immunity · doi:10.1128/iai.68.3.1696-1699.2000 · Cited by 49
“PI 3-kinase inhibitors have been shown to prevent complete formation of macropinosomes (2).”
BackgroundCtBP1/BARS is an activator of phospholipase D1 necessary for agonist‐induced macropinocytosis
Haga, Y., Miwa, N., Jahangeer, S. M., Okada, T., & Nakamura, S. (2009) · The EMBO Journal · doi:10.1038/emboj.2009.78 · Cited by 48
“…process of macropinocytosis, the formation 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 signalling (Araki et al, 1996, 2000, 2003; Anton et al, 2003).”
BackgroundMacropinosomes 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
Self-citationFrom Pinocytosis to Methuosis—Fluid Consumption as a Risk Factor for Cell Death
Ritter, M., Bresgen, N., & Kerschbaum, H. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.651982 · Cited by 51
Kim, S., Watarai, M., Makino, S.-I., & Shirahata, T. (2002) · Microbial Pathogenesis · doi:10.1006/mpat.2002.0531 · Cited by 48
Phosphoinositide 3-Kinases and the Regulation of Vesicular Trafficking
Backer, J. (2000) · Molecular Cell Biology Research Communications · doi:10.1006/mcbr.2000.0202 · Cited by 48
Rate and extent of phagocytosis in macrophages lacking vamp3
Allen, L. H., Yang, C., & Pessin, J. E. (2002) · Journal of Leukocyte Biology · doi:10.1189/jlb.72.1.217 · Cited by 48
Sardo, C., Farra, R., Licciardi, M., Dapas, B., Scialabba, C., Giammona, G., Grassi, M., Grassi, G., & Cavallaro, G. (2015) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2015.03.021 · Cited by 47
Methamphetamine induces macropinocytosis in differentiated SH-SY5Y human neuroblastoma cells
Nara, A., Aki, T., Funakoshi, T., & Uemura, K. (2010) · Brain Research · doi:10.1016/j.brainres.2010.07.043 · Cited by 46
“…known as an actin-dependent endocytic mechanism that leads to internalization of fluid and membrane into large vesicles as macropinosomes, which normally appear with a diameter of 0.5–10 μm (Araki et al., 1996; Doherty and McMahon, 2009; Li et al., 2010; Overmeyer et al., 2008; Wadia et al., 2009).”
InfluentialRole of antibodies in controlling dengue virus infection
van der Schaar, H. M., Wilschut, J., & Smit, J. M. (2009) · Immunobiology · doi:10.1016/j.imbio.2008.11.008 · Cited by 51
“In both cases, the closure of the membrane to form a sealed vacuole, called a phagosome, is mediated by the enzyme phosphoinositide 3-kinase (Araki et al., 1996).”
BackgroundTamura, N., Hazeki, K., Okazaki, N., Kametani, Y., Murakami, H., Takaba, Y., Ishikawa, Y., Nigorikawa, K., & Hazeki, O. (2009) · Biochemical Journal · doi:10.1042/bj20090687 · Cited by 48
Cellular endocytosis and trafficking of cholera toxin B-modified mesoporous silica nanoparticles
Walker, W. A., Tarannum, M., & Vivero-Escoto, J. L. (2016) · Journal of Materials Chemistry B · doi:10.1039/c5tb02079d · Cited by 47
Molecular Mechanisms of Phagosome Formation
Jaumouillé, V., & Grinstein, S. (2016) · Microbiology Spectrum · doi:10.1128/microbiolspec.mchd-0013-2015 · Cited by 51
“Interestingly, PI3K has a much more important role in the phagocytosis of large particles (>3 μm) than of small ones (56, 106).”
BackgroundToxoplasma gondii Mechanisms of Entry Into Host Cells
Portes, J. D. A., Barrias, E., Travassos, R., Attias, M., & de Souza, W. (2020) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2020.00294 · Cited by 47
“On the other hand, the remodeling of the cytoskeleton, characteristic of macropinocytosis, requires activity of phosphatidylinositol-3-kinase (PI3K) at the plasmamembrane (Araki et al., 1996; Rupper et al., 2001; Lindmo and Stenmark, 2006).”
BackgroundAllen, L. H., Allgood, J. A., Han, X., & Wittine, L. M. (2005) · Journal of Leukocyte Biology · doi:10.1189/jlb.0205091 · Cited by 47
“In this context, 3 -phophoinositides regulate pseudopod extension and closure of phagosomes containing large IgG-coated particles but are dispensable for local actin polymerization [14, 15].”
BackgroundResultKarakesisoglou, I., Janssen, K., Eichinger, L., Noegel, A. A., & Schleicher, M. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.145.1.167 · Cited by 47
“Knocking out the PI3-kinases in macrophages inhibited the completion of macropinocytosis and phagocytosis (Araki et al., 1996).”
Inhibition of kinases impairs neutrophil activation and killing of Staphylococcus aureus
Schnyder, B., Meunier, P. C., & Car, B. D. (1998) · Biochemical Journal · doi:10.1042/bj3310489 · Cited by 48
Ferracini, M., Martins, J. O., Campos, M. R. M., Anger, D. B. C., & Jancar, S. (2010) · Molecular Immunology · doi:10.1016/j.molimm.2010.04.018 · Cited by 46
The motor protein myosin 1G functions in FcγR-mediated phagocytosis
Dart, A., Tollis, S., Bright, M. D., Frankel, G. M., & Endres, R. G. (2012) · Journal of Cell Science · doi:10.1242/jcs.109561 · Cited by 46
“In addition, ITAM phosphorylation leads to the recruitment and activation of phosphoinositide 3-kinases (PI3Ks) (Araki et al., 1996; Cox et al., 1999), which convert the lipid substrate phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] to the product phosphatidylinositol (3,4,5)- triphosphate…”
BackgroundInfluentialPhotoreceptor phagocytosis is mediated by phosphoinositide signaling
Mustafi, D., Kevany, B. M., Genoud, C., Bai, X., & Palczewski, K. (2013) · The FASEB Journal · doi:10.1096/fj.13-237537 · Cited by 46
Arf6, JIP3, and dynein shape and mediate macropinocytosis
Williamson, C. D., & Donaldson, J. G. (2019) · Molecular Biology of the Cell · doi:10.1091/mbc.e19-01-0022 · Cited by 46
Phagocytosis of Wild-TypeLegionella pneumophilaOccurs through a Wortmannin-Insensitive Pathway
Khelef, N., Shuman, H. A., & Maxfield, F. R. (2001) · Infection and Immunity · doi:10.1128/iai.69.8.5157-5161.2001 · Cited by 46
“through Fc receptors (20) and macropinocytosis (1), we eval-”
InfluentialLY-294002-inhibitable PI 3-kinase and regulation of baseline rates of Na+ transport in A6 epithelia
Păunescu, T. G., Blazer‐Yost, B. L., Vlahos, C. J., & Helman, S. I. (2000) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.2000.279.1.c236 · Cited by 46
“There are, however, a large number of studies that describe how PI 3-kinase plays a crucial role in endocytotic and/or exocytotic phenomena (2, 6, 8, 9, 16, 23, 24, 33, 38) [see also reviews by Shepherd et al.”
BackgroundCell surface protein aggregation triggers endocytosis to maintain plasma membrane proteostasis
Paul, D., Stern, O., Vallis, Y., Dhillon, J., Buchanan, A. G., & McMahon, H. T. (2023) · Nature Communications · doi:10.1038/s41467-023-36496-y · Cited by 50
Barthwal, M. K., Anzinger, J. J., Xu, Q., Bohnacker, T., Wymann, M. P., & Kruth, H. S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0058054 · Cited by 46
“Previous reports show that inhibition of the PI3K family with wortmannin or LY294002 inhibits murine M-CSF-differentiated bone marrow-derived macrophage macropinocytosis [26,27].”
BackgroundResultMicroRNAs-103/107 coordinately regulate macropinocytosis and autophagy
Park, J. K., Peng, H., Katsnelson, J., Yang, W., Kaplan, N., Dong, Y., Rappoport, J. Z., He, C., & Lavker, R. M. (2016) · The Journal of Cell Biology · doi:10.1083/jcb.201604032 · Cited by 45
Ubiquitous macropinocytosis in anthozoans
Ganot, P., Tambutté, É., Caminiti-Segonds, N., Toullec, G., Allemand, D., & Tambutté, S. (2020) · eLife · doi:10.7554/elife.50022 · Cited by 44
“Macropinocytosis is also a Phosphoinositide 3-kinase (PI3K) dependent process in eukaryotes (Araki et al., 1996; Williams and Kay, 2018), and blocking PI3K with wortmannin inhibited macropinocytosis (Figure 8).”
BackgroundPinton, L., Magri, S., Masetto, E., Vettore, M., Schibuola, I., Ingangi, V., Marigo, I., Matha, K., Benoît, J., Puppa, A. D., et al. (2020) · Journal of Nanobiotechnology · doi:10.1186/s12951-020-00589-3 · Cited by 45
Anzinger, J. J., Chang, J., Xu, Q., Barthwal, M. K., Bohnacker, T., Wymann, M. P., & Kruth, H. S. (2011) · Journal of Lipid Research · doi:10.1194/jlr.m018887 · Cited by 43
Ahram, M. A., Sameni, M., Qiu, R., Linebaugh, B. E., Kirn, D. H., & Sloane, B. F. (2000) · Experimental Cell Research · doi:10.1006/excr.2000.5031 · Cited by 45
da Silva, R. A. G., Tay, W. H., Ho, F. K., Tanoto, F. R., Chong, K. K. L., Choo, P. Y., Ludwig, A., & Kline, K. A. (2022) · PLoS Pathogens · doi:10.1371/journal.ppat.1010434 · Cited by 44
Ferguson, M. S., Chard, L. S., Gangeswaran, R., Marelli, G., Tysome, J. R., Burns, E., Whitehead, M. A., Aksoy, E., Alusi, G., Hiley, C. T., et al. (2020) · Molecular Therapy · doi:10.1016/j.ymthe.2020.02.017 · Cited by 44
“evidence support the importance of the PI3K signaling enzymes in macrophage phagocytosis.(8,11,12) Among the class I PI3K isoforms (PI3Ka, PI3Kb, PI3Kd, PI3Kg), PI3Kd and PI3Kg are highly enriched in leukocytes, including in macrophages.”
Buckley, C. M. F., Pots, H., Guého, A., Vines, J. H., Munn, C. J., Phillips, B. A., Gilsbach, B. K., Traynor, D., Nikolaev, A., Soldati, T., et al. (2020) · Current Biology · doi:10.1016/j.cub.2020.05.049 · Cited by 47
SNX5 is essential for efficient macropinocytosis and antigen processing in primary macrophages
Lim, J. P., Teasdale, R. D., & Gleeson, P. A. (2012) · Biology Open · doi:10.1242/bio.20122204 · Cited by 43
“The downstream targets of phosphoinositide (PI) 3- kinase signalling, namely phosphoinositides, have been shown to be critical in the biogenesis of macropinosomes (Amyere et al., 2000; Anzinger et al., 2012; Araki et al., 1996; Clague et al., 1995; Kerr et al., 2010).”
BackgroundVälimäki, E., Miettinen, J. J., Lietzén, N., Matikainen, S., & Nyman, T. A. (2013) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m112.024661 · Cited by 43
Egami, Y., & Araki, N. (2012) · PLoS ONE · doi:10.1371/journal.pone.0035663 · Cited by 44
“Phagocytosis and phagosome maturation Seep erythrocytes were opsonized with rabbit anti-sheep erythrocyte IgG (1:250, Organo Teknika-Cappel) and resuspended in PBS as described previously [5].”
MethodSelf-citationBakke, O., & Nordeng, T. W. (1999) · Immunological Reviews · doi:10.1111/j.1600-065x.1999.tb01365.x · Cited by 43
Zhang, Y., Liang, R., Wang, S., Ye, Z., Wang, T.-Y., Chen, M., Liu, J., Lei, N., Yang, Y., Yang, Y., et al. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102511 · Cited by 47
“In addition, LY294002, a PI3K inhibitor that blocks macropinosome closure, was included for testing (32).”
Glucksam, Y., Zor, T., & Margalit, R. (2011) · Journal of Controlled Release · doi:10.1016/j.jconrel.2011.10.008 · Cited by 42
“We also explored the effects of inhibitors—2-deoxyglucose (2DOG), LY294002 (LY2) and Wortmannin (Wt)—known to influence particle internalization by macrophages [1,21,22].”
BackgroundDeLoid, G. M., Sulahian, T. H., Imrich, A., & Kobzik, L. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006209 · Cited by 43
“The signaling events and cytoskeletal elements and activities involved in FccR-mediated and CR-mediated phagocytosis have been fairly well characterized [22–34].”
BackgroundShin, B., Suzuki, M., Inukai, K., Anai, M., Asano, T., & Takata, K. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.8606 · Cited by 42
Atypical Protein Kinase C-ζ Is Essential for Delayed Phagocytosis of Helicobacter pylori
Allen, L. H., & Allgood, J. A. (2002) · Current Biology · doi:10.1016/s0960-9822(02)01216-2 · Cited by 42
Rupper, A. C., Rodriguez‐Paris, J., Grove, B. D., & Cardelli, J. A. (2001) · Journal of Cell Science · doi:10.1242/jcs.114.7.1283 · Cited by 42
García‐Pérez, B. E., la Cruz-López, J. J. D., Castañeda‐Sánchez, J. I., Muñóz-Duarte, A. R., Hernández‐Pérez, A. D., Villegas-Castrejón, H., Garcı́a-Latorre, E., Caamal-Ley, Á. D., & Luna‐Herrera, J. (2012) · BMC Microbiology · doi:10.1186/1471-2180-12-246 · Cited by 41
“(WORT), a PI3K inhibitor [23] and (c) 3 μM cytochalasin D (CD), a known inhibitor of actin polymerisation [24].”
BackgroundTan, L., Zhang, Y., Zhan, Y., Yuan, Y., Sun, Y., Qiu, X., Meng, C., Song, C., Liao, Y., & Ding, C. (2016) · Oncotarget · doi:10.18632/oncotarget.13345 · Cited by 41
Akishiba, M., & Futaki, S. (2019) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.9b00156 · Cited by 41
Phagocytosis is mediated by two-dimensional assemblies of the F-BAR protein GAS7
Hanawa‐Suetsugu, K., Itoh, Y., Fatah, M. A., Nishimura, T., Takemura, K., Takeshita, K., Kubota, S., Miyazaki, N., Noor, W. N. I. W. M., Inaba, T., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-12738-w · Cited by 40
Zhang, X., Mi, J., Wetsel, W. C., Davidson, C., Xiong, X., Chen, Q., Ellinwood, E. H., & Lee, T. H. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.12.114 · Cited by 41
Clayton, E. L., & Cousin, M. A. (2009) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2009.09.016 · Cited by 41
“Fluorescent-tagged dextrans are too large to be internalised within a single SV (Berthiaume et al., 1995; Araki et al., 1996; Holt et al., 2003; Teng et al., 2007).”
Nara, A., Aki, T., Funakoshi, T., Unuma, K., & Uemura, K. (2012) · Brain Research · doi:10.1016/j.brainres.2012.05.017 · Cited by 40
Kato, T., Kawai, K., Egami, Y., Kakehi, Y., & Araki, N. (2014) · PLoS ONE · doi:10.1371/journal.pone.0097749 · Cited by 40
“However, PI3K activity is reportedly unnecessary for M-CSF-induced ruffling and EGFinduced dorsal ruffling in A431 cells [22,23].”
BackgroundSelf-citationGrinstein, S. (2010) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00342.2010 · Cited by 39
“, using the PLC inhibitor U73122) arrests phagocytosis (1, 9), as does the overexpression or enforced retention of phosphatidylinositol 4-phosphate 5 kinase at the phagosomal cup, as Gregory Fairn found (4).”
MethodKumar, B., Dutta, D., Iqbal, J., Ansari, M. A., Roy, A., Leela, C., Pisano, G., Veettil, M. V., & Chandran, B. (2016) · PLoS Pathogens · doi:10.1371/journal.ppat.1005960 · Cited by 39
Kim, B., Lee, J. H., Seo, M., Eom, S. H., & Kim, W. (2016) · Food Science and Biotechnology · doi:10.1007/s10068-016-0223-3 · Cited by 41
Syk and Src-targeted anti-inflammatory activity of aripiprazole, an atypical antipsychotic
Yoo, S., Kim, M., & Cho, J. Y. (2017) · Biochemical Pharmacology · doi:10.1016/j.bcp.2017.12.006 · Cited by 40
“To determine if ARP affected phagocytosis, an essential process in immune responses for removing extracellular pathogens [33], RAW264.”
BackgroundZiemba, B. P., & Falke, J. J. (2018) · PLoS ONE · doi:10.1371/journal.pone.0196678 · Cited by 45
Flak, D., Przysiecka, Ł., Nowaczyk, G., Scheibe, B., Kościński, M., Jesionowski, T., & Jurga, S. (2018) · Journal of Nanoparticle Research · doi:10.1007/s11051-018-4416-y · Cited by 40
AMP-Activated Protein Kinase Is Required for the Macropinocytic Internalization of Ebolavirus
Kondratowicz, A. S., Hunt, C. L., Davey, R. A., Cherry, S. R., & Maury, W. J. (2012) · Journal of Virology · doi:10.1128/jvi.01634-12 · Cited by 40
Host adaptor proteins Gab1 and CrkII promote InlB-dependent entry of Listeria monocytogenes
Sun, H., Shen, Y., Dokainish, H., Holgado-Madruga, M., Wong, A. J., & Ireton, K. (2005) · Cellular Microbiology · doi:10.1111/j.1462-5822.2004.00475.x · Cited by 40
“By analogy to its demonstrated roles in ‘classic’ Fc-g receptor-mediated phagocytosis (Araki et al., 1996; Cox et al., 1999; Vieira et al., 2001; Greenberg and Grinstein, 2002), it is possible that p85-p110 promotes extension and sealing of ‘pseudopodia’ (finger-like projections of the host plasma membrane) around adh…”
BackgroundLee, J. S., Nauseef, W. M., Moeenrezakhanlou, A., Sly, L. M., Noubir, S., Leidal, K. G., Schlomann, J. M., Krystal, G., & Reiner, N. E. (2007) · Journal of Leukocyte Biology · doi:10.1189/jlb.0906564 · Cited by 42
“PI-3K has been demonstrated to be an important regulator of Fc R and CR3-mediated phagocytosis [2, 23], but the specific isoform of PI-3K involved in mediating these events in human monocytic cells is not clear.”
BackgroundLowry, M. B., Duchemin, A., Coggeshall, K. M., Robinson, J. M., & Anderson, C. L. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.38.24513 · Cited by 40
Bulloj, A., Duan, W., & Finnemann, S. C. (2013) · Experimental Eye Research · doi:10.1016/j.exer.2013.05.002 · Cited by 39
“In macrophages, PI3K inhibition by LY294002 reduces phagocytosis by impeding phagocytic cup closure but not by blocking phagocytic cup formation (Araki et al., 1996).”
InfluentialConserved features of endocytosis in Dictyostelium
Maniak, M. (2002) · International Review of Cytology · doi:10.1016/s0074-7696(02)21014-1 · Cited by 52
Horan, K. A., Watanabe, K.-I., Kong, A. M., Bailey, C. G., Rasko, J. E. J., Sasaki, T., & Mitchell, C. A. (2007) · Blood · doi:10.1182/blood-2007-02-073874 · Cited by 45
Macropinocytosis and Cancer: From Tumor Stress to Signaling Pathways
Lambies, G., & Commisso, C. (2022) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-3-030-94004-1_2 · Cited by 43
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
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