phospholipase c gamma


Summary: A phosphoinositide phospholipase C subtype that is primarily regulated by PROTEIN-TYROSINE KINASES. It is structurally related to PHOSPHOLIPASE C DELTA with the addition of SRC HOMOLOGY DOMAINS and pleckstrin homology domains located between two halves of the CATALYTIC DOMAIN.

Top Publications

  1. Kim K, Wang L, Hwang I. LFA-1-dependent Ca2+ entry following suboptimal T cell receptor triggering proceeds without mobilization of intracellular Ca2+. J Biol Chem. 2009;284:22149-54 pubmed publisher
    ..These results ensure the unique role of LFA-1 in T cell Ca2+ signaling and reveal that LFA-1-dependent Ca2+ entry proceeds via a mechanism separate from store-operated Ca2+ entry. ..
  2. Sala G, Dituri F, Raimondi C, Previdi S, Maffucci T, Mazzoletti M, et al. Phospholipase Cgamma1 is required for metastasis development and progression. Cancer Res. 2008;68:10187-96 pubmed publisher
    ..These data show a critical role of PLCgamma1 in the metastatic potential of cancer cells, and they further indicate that PLCgamma1 inhibition has a therapeutic potential in the treatment of metastasis dissemination. ..
  3. Ichise H, Ichise T, Ohtani O, Yoshida N. Phospholipase Cgamma2 is necessary for separation of blood and lymphatic vasculature in mice. Development. 2009;136:191-5 pubmed publisher
    ..These findings indicate that PLCgamma2 plays an essential role in initiating and maintaining the separation of the blood and lymphatic vasculature. ..
  4. Epple H, Cremasco V, Zhang K, Mao D, Longmore G, Faccio R. Phospholipase Cgamma2 modulates integrin signaling in the osteoclast by affecting the localization and activation of Src kinase. Mol Cell Biol. 2008;28:3610-22 pubmed publisher
    ..Here, we demonstrate an important role for phospholipase C gamma 2 (PLCgamma2) in Src activation in the osteoclast...
  5. Hughes C, Pollitt A, Mori J, Eble J, Tomlinson M, Hartwig J, et al. CLEC-2 activates Syk through dimerization. Blood. 2010;115:2947-55 pubmed publisher
    ..This is a unique mode of activation of Syk by a single YxxL-containing receptor. ..
  6. Gresset A, Hicks S, Harden T, Sondek J. Mechanism of phosphorylation-induced activation of phospholipase C-gamma isozymes. J Biol Chem. 2010;285:35836-47 pubmed publisher
    ..Consequently, PLC-? isozymes link phosphorylation to phospholipase activation by elaborating upon primordial regulatory mechanisms found in other PLCs. ..
  7. Sadagopan S, Valiya Veettil M, Paudel N, Bottero V, Chandran B. Kaposi's sarcoma-associated herpesvirus-induced angiogenin plays roles in latency via the phospholipase C gamma pathway: blocking angiogenin inhibits latent gene expression and induces the lytic cycle. J Virol. 2011;85:2666-85 pubmed publisher
    ..Taken together, these studies suggest that KSHV has evolved to exploit ANG for its advantage via a so-far-unexplored PLC-? pathway for maintaining its latency. ..
  8. Weber M, Treanor B, Depoil D, Shinohara H, Harwood N, Hikida M, et al. Phospholipase C-gamma2 and Vav cooperate within signaling microclusters to propagate B cell spreading in response to membrane-bound antigen. J Exp Med. 2008;205:853-68 pubmed publisher
    ..Thus, we demonstrate the importance of cooperation between components of the microsignalosome in the amplification of signaling and propagation of B cell spreading, which is critical for appropriate B cell activation. ..
  9. Carrizosa E, Gomez T, Labno C, Klos Dehring D, Liu X, Freedman B, et al. Hematopoietic lineage cell-specific protein 1 is recruited to the immunological synapse by IL-2-inducible T cell kinase and regulates phospholipase Cgamma1 Microcluster dynamics during T cell spreading. J Immunol. 2009;183:7352-61 pubmed publisher
    ..We conclude that HS1 functions as an effector of Itk in the T cell actin-regulatory pathway, and directs the spatial organization of PLCgamma1 signaling complexes. ..

More Information


  1. Harita Y, Kurihara H, Kosako H, Tezuka T, Sekine T, Igarashi T, et al. Phosphorylation of Nephrin Triggers Ca2+ Signaling by Recruitment and Activation of Phospholipase C-{gamma}1. J Biol Chem. 2009;284:8951-62 pubmed publisher
    ..Given the profound effect of PLC-gamma in diverse cellular functions, regulation of the Ca(2+) signaling by Nephrin may be important in modulating the glomerular filtration barrier function. ..
  2. Walliser C, Retlich M, Harris R, Everett K, Josephs M, Vatter P, et al. rac regulates its effector phospholipase Cgamma2 through interaction with a split pleckstrin homology domain. J Biol Chem. 2008;283:30351-62 pubmed publisher
    ..We further discuss parallels and differences between PLCgamma(1) and PLCgamma(2) and the implications of our findings for their respective signaling roles. ..
  3. Zhang K, Kim S, Cremasco V, Hirbe A, Collins L, Piwnica Worms D, et al. CD8+ T cells regulate bone tumor burden independent of osteoclast resorption. Cancer Res. 2011;71:4799-808 pubmed publisher
    ..Our findings show the important contribution of CD8(+) T cells in the regulation of bone metastases regardless of OC status, thus including T cells as critical regulators of tumor growth in bone. ..
  4. Xie Z, Chang S, Pennypacker S, Liao E, Bikle D. Phosphatidylinositol-4-phosphate 5-kinase 1alpha mediates extracellular calcium-induced keratinocyte differentiation. Mol Biol Cell. 2009;20:1695-704 pubmed publisher
    ..This signaling pathway is critical for Cao-induced generation of the second messengers IP3 and Cai and keratinocyte differentiation. ..
  5. Townley I, Schuyler E, Parker G r M, Foltz K. Expression of multiple Src family kinases in sea urchin eggs and their function in Ca2+ release at fertilization. Dev Biol. 2009;327:465-77 pubmed publisher
    ..Collectively, these data indicate that more than one SFK is involved in the Ca(2+) release pathway at fertilization...
  6. Feng L, Reynisdottir I, Reynisson J. The effect of PLC-?2 inhibitors on the growth of human tumour cells. Eur J Med Chem. 2012;54:463-9 pubmed publisher
    ..The compounds tested were identified by applying the tools of chemoinformatics, which supports the use of in silico methods in drug design. ..
  7. Swiercz J, Worzfeld T, Offermanns S. Semaphorin 4D signaling requires the recruitment of phospholipase C gamma into the plexin-B1 receptor complex. Mol Cell Biol. 2009;29:6321-34 pubmed publisher
  8. Sherman E, Barr V, Manley S, Patterson G, Balagopalan L, Akpan I, et al. Functional nanoscale organization of signaling molecules downstream of the T cell antigen receptor. Immunity. 2011;35:705-20 pubmed publisher
    ..These results extend our understanding of the mechanism of T cell activation and the formation and organization of TCR-mediated signaling complexes, findings also relevant to other receptor systems. ..
  9. Bezman N, Lian L, Abrams C, Brass L, Kahn M, Jordan M, et al. Requirements of SLP76 tyrosines in ITAM and integrin receptor signaling and in platelet function in vivo. J Exp Med. 2008;205:1775-88 pubmed publisher
    ..Using genetic complementation, we further demonstrate that all three phosphorylatable tyrosines are required within the same SLP76 molecule to support platelet activation by GPVI. ..
  10. Dong Z, Davidson D, Pérez Quintero L, Kurosaki T, Swat W, Veillette A. The adaptor SAP controls NK cell activation by regulating the enzymes Vav-1 and SHIP-1 and by enhancing conjugates with target cells. Immunity. 2012;36:974-85 pubmed publisher
    ..These data showed that SAP secures NK cell activation by a dichotomous molecular mechanism, which is required for conjugate formation. These findings may have implications for the role of SAP in other immune cell types. ..
  11. Block H, Herter J, Rossaint J, Stadtmann A, Kliche S, Lowell C, et al. Crucial role of SLP-76 and ADAP for neutrophil recruitment in mouse kidney ischemia-reperfusion injury. J Exp Med. 2012;209:407-21 pubmed publisher
    ..Thus, SLP-76 and ADAP are involved in E-selectin-mediated integrin activation and neutrophil recruitment to inflamed kidneys, which may underlie the development of life-threatening ischemia-reperfusion-induced AKI in humans...
  12. Bunney T, Opaleye O, Roe S, Vatter P, Baxendale R, Walliser C, et al. Structural insights into formation of an active signaling complex between Rac and phospholipase C gamma 2. Mol Cell. 2009;34:223-33 pubmed publisher
  13. Tassi I, Cella M, Castro I, Gilfillan S, Khan W, Colonna M. Requirement of phospholipase C-gamma2 (PLCgamma2) for Dectin-1-induced antigen presentation and induction of TH1/TH17 polarization. Eur J Immunol. 2009;39:1369-78 pubmed publisher
    ..We conclude that PLCgamma2 is a crucial signaling mediator that modifies DC gene expression program to activate DC responses to beta-glucan-containing pathogens. ..
  14. Lin K, Chang Y, Fan C, Jayakumar T, Lee J, Chou D, et al. Arsenic trioxide-mediated antiplatelet activity: pivotal role of the phospholipase C gamma 2-protein kinase C-p38 MAPK cascade. Transl Res. 2010;155:97-108 pubmed publisher
  15. Xie Z, Peng J, Pennypacker S, Chen Y. Critical role for the catalytic activity of phospholipase C-gamma1 in epidermal growth factor-induced cell migration. Biochem Biophys Res Commun. 2010;399:425-8 pubmed publisher
    ..These data indicate that EGF-induced cell migration is mediated by the lipase domain of PLC-gamma1 and the subsequent IP(3) generation and intracellular calcium mobilization. ..
  16. Chen Y, Wang X, Di L, Fu G, Chen Y, Bai L, et al. Phospholipase Cgamma2 mediates RANKL-stimulated lymph node organogenesis and osteoclastogenesis. J Biol Chem. 2008;283:29593-601 pubmed publisher
    ..Taken together, PLCgamma2 is essential for RANK signaling, and its deficiency leads to defective lymph node organogenesis and osteoclast differentiation. ..
  17. Fu G, Chen Y, Yu M, Podd A, Schuman J, He Y, et al. Phospholipase C{gamma}1 is essential for T cell development, activation, and tolerance. J Exp Med. 2010;207:309-18 pubmed publisher
    ..Importantly, PLCgamma1 deficiency impairs the development and function of FoxP3(+) regulatory T cells, causing inflammatory/autoimmune symptoms. Therefore, PLCgamma1 is essential for T cell development, activation, and tolerance. ..
  18. Abe K, Fuchs H, Boersma A, Hans W, Yu P, Kalaydjiev S, et al. A novel N-ethyl-N-nitrosourea-induced mutation in phospholipase C?2 causes inflammatory arthritis, metabolic defects, and male infertility in vitro in a murine model. Arthritis Rheum. 2011;63:1301-11 pubmed publisher
    ..These findings may indicate the importance of the Ali14/+ mouse strain as a model for systemic inflammatory diseases and inflammation-related metabolic changes in humans. ..
  19. Zhang P, Zhao Y, Zhu X, Sedwick D, Zhang X, Wang Z. Cross-talk between phospho-STAT3 and PLC?1 plays a critical role in colorectal tumorigenesis. Mol Cancer Res. 2011;9:1418-28 pubmed publisher
    ..In aggregate, our study identifies previously unknown cross-talk between STAT3 and the PLC? signaling pathways that may play a critical role in colorectal tumorigenesis. ..
  20. Clarkson N, Brown M. Inhibition and activation by CD244 depends on CD2 and phospholipase C-gamma1. J Biol Chem. 2009;284:24725-34 pubmed publisher
    ..We identify a novel signaling mechanism for CD244 through its potential to recruit phospholipase C-gamma1 via the conserved phosphorylated tyrosine motif in the tail of the adaptor protein EAT-2, which we show is important for function. ..
  21. Covassin L, Siekmann A, Kacergis M, Laver E, Moore J, Villefranc J, et al. A genetic screen for vascular mutants in zebrafish reveals dynamic roles for Vegf/Plcg1 signaling during artery development. Dev Biol. 2009;329:212-26 pubmed publisher
    ..In parallel, we identified an allelic series of mutations in phospholipase c gamma 1 (plcg1)...
  22. Jing C, Chen Y, Dong M, Peng X, Jia X, Gao L, et al. Phospholipase C gamma-1 is required for granulocyte maturation in zebrafish. Dev Biol. 2013;374:24-31 pubmed publisher
    ..Positional cloning revealed that phospholipase C gamma-1 (plcg1) was mutated...
  23. Cremasco V, Benasciutti E, Cella M, Kisseleva M, Croke M, Faccio R. Phospholipase C gamma 2 is critical for development of a murine model of inflammatory arthritis by affecting actin dynamics in dendritic cells. PLoS ONE. 2010;5:e8909 pubmed publisher
  24. Bunney T, Esposito D, Mas Droux C, Lamber E, Baxendale R, Martins M, et al. Structural and functional integration of the PLC? interaction domains critical for regulatory mechanisms and signaling deregulation. Structure. 2012;20:2062-75 pubmed publisher
  25. Zhou Q, Lee G, Brady J, Datta S, Katan M, Sheikh A, et al. A hypermorphic missense mutation in PLCG2, encoding phospholipase Cγ2, causes a dominantly inherited autoinflammatory disease with immunodeficiency. Am J Hum Genet. 2012;91:713-20 pubmed publisher
    ..Our results highlight the utility of exome-sequencing technology in finding causal mutations in nuclear families with dominantly inherited traits otherwise intractable by linkage analysis. ..
  26. Jakus Z, Simon E, Frommhold D, Sperandio M, Mócsai A. Critical role of phospholipase Cgamma2 in integrin and Fc receptor-mediated neutrophil functions and the effector phase of autoimmune arthritis. J Exp Med. 2009;206:577-93 pubmed publisher
    ..These results identify PLCgamma2 as a critical player of integrin and Fc receptor-mediated neutrophil functions and the neutrophil-mediated effector phase of autoimmune arthritis. ..
  27. Dumas F, Byrne R, Vincent B, Hobday T, Poccia D, Larijani B. Spatial regulation of membrane fusion controlled by modification of phosphoinositides. PLoS ONE. 2010;5:e12208 pubmed publisher
    ..We discuss the general implications of membrane fusion regulation and spatial control utilising such a mechanism. ..
  28. Stadtmann A, Brinkhaus L, Mueller H, Rossaint J, Bolomini Vittori M, Bergmeier W, et al. Rap1a activation by CalDAG-GEFI and p38 MAPK is involved in E-selectin-dependent slow leukocyte rolling. Eur J Immunol. 2011;41:2074-85 pubmed publisher
    ..Our data demonstrate that Rap1a activation by p38 MAPK and CalDAG-GEFI is involved in E-selectin-dependent slow rolling and leukocyte recruitment. ..
  29. Everett K, Bunney T, Yoon Y, Rodrigues Lima F, Harris R, Driscoll P, et al. Characterization of phospholipase C gamma enzymes with gain-of-function mutations. J Biol Chem. 2009;284:23083-93 pubmed publisher
    b>Phospholipase C gamma isozymes (PLC gamma 1 and PLC gamma 2) have a crucial role in the regulation of a variety of cellular functions. Both enzymes have also been implicated in signaling events underlying aberrant cellular responses...
  30. Cremasco V, Graham D, Novack D, Swat W, Faccio R. Vav/Phospholipase Cgamma2-mediated control of a neutrophil-dependent murine model of rheumatoid arthritis. Arthritis Rheum. 2008;58:2712-22 pubmed publisher
    ..This study identifies a Vav/PLCgamma2-dependent signaling pathway as a possible therapeutic target for the treatment of inflammation and bone disruption in arthritis. ..
  31. Zachos N, van Rossum D, Li X, Caraveo G, Sarker R, Cha B, et al. Phospholipase C-gamma binds directly to the Na+/H+ exchanger 3 and is required for calcium regulation of exchange activity. J Biol Chem. 2009;284:19437-44 pubmed publisher
    ..These results mirror previous studies with the transient receptor potential channel and suggest that PLC-gamma may play a common role in regulating the cell-surface expression of ion transporters. ..
  32. Ombrello M, Remmers E, Sun G, Freeman A, Datta S, Torabi Parizi P, et al. Cold urticaria, immunodeficiency, and autoimmunity related to PLCG2 deletions. N Engl J Med. 2012;366:330-8 pubmed publisher
    ..Funded by the National Institutes of Health Intramural Research Programs and others.). ..
  33. Everett K, Buehler A, Bunney T, Margineanu A, Baxendale R, Vatter P, et al. Membrane environment exerts an important influence on rac-mediated activation of phospholipase C?2. Mol Cell Biol. 2011;31:1240-51 pubmed publisher
  34. Mueller H, Stadtmann A, Van Aken H, Hirsch E, Wang D, Ley K, et al. Tyrosine kinase Btk regulates E-selectin-mediated integrin activation and neutrophil recruitment by controlling phospholipase C (PLC) gamma2 and PI3Kgamma pathways. Blood. 2010;115:3118-27 pubmed publisher
    ..Our data demonstrate the functional importance of this newly identified signaling pathway mediated by E-selectin engagement. ..
  35. Mori J, Pearce A, Spalton J, Grygielska B, Eble J, Tomlinson M, et al. G6b-B inhibits constitutive and agonist-induced signaling by glycoprotein VI and CLEC-2. J Biol Chem. 2008;283:35419-27 pubmed publisher
    ..We speculate that inhibition of constitutive signaling through Src and Syk tyrosine kinases by G6b-B may help to prevent unwanted platelet activation. ..
  36. Caraveo G, van Rossum D, Patterson R, Snyder S, Desiderio S. Action of TFII-I outside the nucleus as an inhibitor of agonist-induced calcium entry. Science. 2006;314:122-5 pubmed
    ..Our observations suggest a model in which TFII-I suppresses ACE by competing with TRPC3 for binding to PLC-g. ..
  37. Shao H, Chou J, Baty C, Burke N, Watkins S, Stolz D, et al. Spatial localization of m-calpain to the plasma membrane by phosphoinositide biphosphate binding during epidermal growth factor receptor-mediated activation. Mol Cell Biol. 2006;26:5481-96 pubmed
  38. Huang Y, Grasis J, Miller A, Xu R, Soonthornvacharin S, Andreotti A, et al. Positive regulation of Itk PH domain function by soluble IP4. Science. 2007;316:886-9 pubmed
    ..Our data suggest that IP4 establishes a feedback loop of phospholipase C-gamma1 activation through Itk that is essential for T cell development. ..
  39. Singh A, Meyer R, Navruzbekov G, Shelke R, Duan L, Band H, et al. A critical role for the E3-ligase activity of c-Cbl in VEGFR-2-mediated PLCgamma1 activation and angiogenesis. Proc Natl Acad Sci U S A. 2007;104:5413-8 pubmed
    ..Our data demonstrate that corecruitment of c-Cbl and PLCgamma1 to VEGFR-2 serves as a mechanism to fine-tune the angiogenic signal relay of VEGFR-2. ..
  40. Dhanjal T, Ross E, Auger J, McCarty O, Hughes C, Senis Y, et al. Minimal regulation of platelet activity by PECAM-1. Platelets. 2007;18:56-67 pubmed
  41. Peng Z, Arendshorst W. Activation of phospholipase C gamma 1 protects renal arteriolar VSMCs from H2O2-induced cell death. Kidney Blood Press Res. 2008;31:1-9 pubmed
  42. El Sibai M, Backer J. Phospholipase C gamma negatively regulates Rac/Cdc42 activation in antigen-stimulated mast cells. Eur J Immunol. 2007;37:261-70 pubmed
    ..These data suggest that PLCgamma is involved in a negative feedback loop that leads to the inhibition of Rac and Cdc42. They also suggest that the presence of intracellular calcium is a prerequisite for both Rac and Cdc42 activation. ..
  43. Mao D, Epple H, Uthgenannt B, Novack D, Faccio R. PLCgamma2 regulates osteoclastogenesis via its interaction with ITAM proteins and GAB2. J Clin Invest. 2006;116:2869-79 pubmed
    ..Thus, PLCgamma2 mediates RANKL-induced osteoclastogenesis and is a potential candidate for antiresorptive therapy...
  44. Tang C, Yang R, Chen Y, Fu W. Basic fibroblast growth factor stimulates fibronectin expression through phospholipase C gamma, protein kinase C alpha, c-Src, NF-kappaB, and p300 pathway in osteoblasts. J Cell Physiol. 2007;211:45-55 pubmed
    ..Our results suggest that bFGF increased Fn expression in rat osteoblasts via the FGFR2/PLCgamma2/PKCalpha/c-Src/NF-kappaB signaling pathway. ..
  45. Jain S, Encinas M, Johnson E, Milbrandt J. Critical and distinct roles for key RET tyrosine docking sites in renal development. Genes Dev. 2006;20:321-33 pubmed
    ..These results reveal novel roles of key RET-dependent signaling pathways in embryonic kidney development and provide murine models and new insights into the molecular basis for CAKUT. ..
  46. Townley I, Roux M, Foltz K. Signal transduction at fertilization: the Ca2+ release pathway in echinoderms and other invertebrate deuterostomes. Semin Cell Dev Biol. 2006;17:293-302 pubmed
    ..In eggs of these animals, Src-type kinases and phospholipase C-gamma are required components of the initial calcium trigger pathway in eggs. ..
  47. Ahmad S, Hewett P, Wang P, Al Ani B, Cudmore M, Fujisawa T, et al. Direct evidence for endothelial vascular endothelial growth factor receptor-1 function in nitric oxide-mediated angiogenesis. Circ Res. 2006;99:715-22 pubmed
    ..These studies provide new sites of modulation in VEGF-mediated vascular morphogenesis and highlight new therapeutic targets for management of vascular diseases. ..
  48. Nolz J, Gomez T, Zhu P, Li S, Medeiros R, Shimizu Y, et al. The WAVE2 complex regulates actin cytoskeletal reorganization and CRAC-mediated calcium entry during T cell activation. Curr Biol. 2006;16:24-34 pubmed
  49. Choi J, Ryu S, Suh P. On/off-regulation of phospholipase C-gamma 1-mediated signal transduction. Adv Enzyme Regul. 2007;47:104-16 pubmed
  50. Lo H, Hung C, Tseng Y, Chen B, Jian J, Wu W. Lycopene binds PDGF-BB and inhibits PDGF-BB-induced intracellular signaling transduction pathway in rat smooth muscle cells. Biochem Pharmacol. 2007;74:54-63 pubmed
    ..The results presented here may help us to better understand the beneficial effects of lycopene in CVD prevention. ..
  51. Ragab A, Severin S, Gratacap M, Aguado E, Malissen M, Jandrot Perrus M, et al. Roles of the C-terminal tyrosine residues of LAT in GPVI-induced platelet activation: insights into the mechanism of PLC gamma 2 activation. Blood. 2007;110:2466-74 pubmed
    ..Thus, activation of PLCgamma2 via GPVI is dependent on 2 complementary events: its interaction with the tyrosine 136 of LAT and its membrane location, which itself requires events mediated by the 3 C-terminal tyrosines of LAT. ..
  52. Aki D, Minoda Y, Yoshida H, Watanabe S, Yoshida R, Takaesu G, et al. Peptidoglycan and lipopolysaccharide activate PLCgamma2, leading to enhanced cytokine production in macrophages and dendritic cells. Genes Cells. 2008;13:199-208 pubmed publisher
    ..Moreover, PLCgamma2 was necessary for the full production of TNF-alpha and IL-6. These data indicate that the PLCgamma2 pathway plays an important role in bacterial ligands-induced activation of macrophages and dendritic cells. ..
  53. DeBell K, Graham L, Reischl I, Serrano C, Bonvini E, Rellahan B. Intramolecular regulation of phospholipase C-gamma1 by its C-terminal Src homology 2 domain. Mol Cell Biol. 2007;27:854-63 pubmed
    ..These data are consistent with a model in which the SH2C domain is blocked by an intramolecular interaction(s) that is released upon cellular activation by occupancy of the SH2N domain. ..