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Gene Review

PLCG1  -  phospholipase C, gamma 1

Homo sapiens

Synonyms: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1, NCKAP3, PLC-148, PLC-II, PLC-gamma-1, ...
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Disease relevance of PLCG1


Psychiatry related information on PLCG1


High impact information on PLCG1


Chemical compound and disease context of PLCG1


Biological context of PLCG1


Anatomical context of PLCG1


Associations of PLCG1 with chemical compounds

  • (1998) recently published preliminary evidence suggesting that bipolar patients with an excellent response to lithium treatment have a higher frequency of a specific dinucleotide repeat allele in the phospholipase Cgamma-1 (PLCG1) genomic region [5].
  • This relocalization and association with Rac1 were impaired by disruption of the beta2-chimaerin C1 domain as well as by PLCgamma1 RNAi, thus defining beta2-chimaerin as a novel DAG effector [16].
  • In addition, the dominant-negative PLC gamma-1 fragment did not diminish EGF-induced thymidine incorporation [21].
  • Characterization of PDGFR mutants in which these phosphorylation sites are substituted with phenylalanine (F) indicated that Y-1021 and Y-1009 were required for the stable association of PLC gamma and a 64-kDa protein, respectively [22].
  • In primary cultures of human mast cells, Fc epsilon RI aggregation induced a rapid translocation and phosphorylation of PLC gamma 1, and subsequent inositol trisphosphate (IP3) production, which preceded PI 3-kinase-related signals [23].

Physical interactions of PLCG1


Enzymatic interactions of PLCG1

  • Indeed, purified PDGF or EGF receptor phosphorylated purified PLC-gamma on tyrosines identical to those phosphorylated in vivo [14].
  • PKC mu can down-regulate the ability of Syk to phosphorylate PLC gamma 1 in vitro [30].
  • The C-terminal half of the PLC-gamma split PH domain has been implicated to interact directly with the TRPC3 calcium channel, thereby providing a direct coupling mechanism between PLC-gamma and agonist-induced calcium entry [31].
  • In addition, phospholipase Cgamma1 (PLCgamma1) and PLCgamma2 were tyrosine phosphorylated upon Ag stimulation in CD45- cells, despite much reduced inositol trisphosphate production and lack of calcium mobilization [32].
  • Unglycosylated TrkA core protein is phosphorylated even in the absence of ligand stimulation and displays constitutive kinase activity as well as constitutive interaction with the signaling molecules Shc and PLC-gamma [33].

Regulatory relationships of PLCG1


Other interactions of PLCG1


Analytical, diagnostic and therapeutic context of PLCG1


  1. Chronic pancreatitis is associated with increased concentrations of epidermal growth factor receptor, transforming growth factor alpha, and phospholipase C gamma. Korc, M., Friess, H., Yamanaka, Y., Kobrin, M.S., Buchler, M., Beger, H.G. Gut (1994) [Pubmed]
  2. The epidermal growth factor receptor is associated with phospholipase C-gamma 1 in meningiomas. Johnson, M.D., Horiba, M., Winnier, A.R., Arteaga, C.L. Hum. Pathol. (1994) [Pubmed]
  3. ShcA and Grb2 mediate polyoma middle T antigen-induced endothelial transformation and Gab1 tyrosine phosphorylation. Ong, S.H., Dilworth, S., Hauck-Schmalenberger, I., Pawson, T., Kiefer, F. EMBO J. (2001) [Pubmed]
  4. Elevated content of the tyrosine kinase substrate phospholipase C-gamma 1 in primary human breast carcinomas. Arteaga, C.L., Johnson, M.D., Todderud, G., Coffey, R.J., Carpenter, G., Page, D.L. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  5. The phospholipase C-gamma1 gene (PLCG1) and lithium-responsive bipolar disorder: re-examination of an intronic dinucleotide repeat polymorphism. Løvlie, R., Berle, J.O., Stordal, E., Steen, V.M. Psychiatr. Genet. (2001) [Pubmed]
  6. Metabotropic glutamate receptor/phospholipase C pathway: a vulnerable target to Creutzfeldt-Jakob disease in the cerebral cortex. Rodríguez, A., Freixes, M., Dalfó, E., Martín, M., Puig, B., Ferrer, I. Neuroscience (2005) [Pubmed]
  7. Compartmentalized ras/mapk signaling. Mor, A., Philips, M.R. Annu. Rev. Immunol. (2006) [Pubmed]
  8. Signal transduction by the B cell antigen receptor and its coreceptors. Cambier, J.C., Pleiman, C.M., Clark, M.R. Annu. Rev. Immunol. (1994) [Pubmed]
  9. The role of the CD28 receptor during T cell responses to antigen. Linsley, P.S., Ledbetter, J.A. Annu. Rev. Immunol. (1993) [Pubmed]
  10. Adenosine 5'-triphosphate: a P2-purinergic agonist in the myocardium. Vassort, G. Physiol. Rev. (2001) [Pubmed]
  11. A multifunctional docking site mediates signaling and transformation by the hepatocyte growth factor/scatter factor receptor family. Ponzetto, C., Bardelli, A., Zhen, Z., Maina, F., dalla Zonca, P., Giordano, S., Graziani, A., Panayotou, G., Comoglio, P.M. Cell (1994) [Pubmed]
  12. Antigen receptor-mediated protein tyrosine kinase activity is regulated by a pertussis toxin-sensitive G protein. Melamed, I., Wang, G., Roifman, C.M. J. Immunol. (1992) [Pubmed]
  13. Kinetics of trkA tyrosine kinase activity and inhibition by K-252a. Angeles, T.S., Yang, S.X., Steffler, C., Dionne, C.A. Arch. Biochem. Biophys. (1998) [Pubmed]
  14. Phospholipase C-gamma is a substrate for the PDGF and EGF receptor protein-tyrosine kinases in vivo and in vitro. Meisenhelder, J., Suh, P.G., Rhee, S.G., Hunter, T. Cell (1989) [Pubmed]
  15. SH2 domains prevent tyrosine dephosphorylation of the EGF receptor: identification of Tyr992 as the high-affinity binding site for SH2 domains of phospholipase C gamma. Rotin, D., Margolis, B., Mohammadi, M., Daly, R.J., Daum, G., Li, N., Fischer, E.H., Burgess, W.H., Ullrich, A., Schlessinger, J. EMBO J. (1992) [Pubmed]
  16. Phospholipase Cgamma/diacylglycerol-dependent activation of beta2-chimaerin restricts EGF-induced Rac signaling. Wang, H., Yang, C., Leskow, F.C., Sun, J., Canagarajah, B., Hurley, J.H., Kazanietz, M.G. EMBO J. (2006) [Pubmed]
  17. Predominant expression and activation-induced tyrosine phosphorylation of phospholipase C-gamma 2 in B lymphocytes. Coggeshall, K.M., McHugh, J.C., Altman, A. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  18. Association of the tyrosine kinase LCK with phospholipase C-gamma 1 after stimulation of the T cell antigen receptor. Weber, J.R., Bell, G.M., Han, M.Y., Pawson, T., Imboden, J.B. J. Exp. Med. (1992) [Pubmed]
  19. Fc gamma receptor activation induces the tyrosine phosphorylation of both phospholipase C (PLC)-gamma 1 and PLC-gamma 2 in natural killer cells. Ting, A.T., Karnitz, L.M., Schoon, R.A., Abraham, R.T., Leibson, P.J. J. Exp. Med. (1992) [Pubmed]
  20. A tyrosine-phosphorylated carboxy-terminal peptide of the fibroblast growth factor receptor (Flg) is a binding site for the SH2 domain of phospholipase C-gamma 1. Mohammadi, M., Honegger, A.M., Rotin, D., Fischer, R., Bellot, F., Li, W., Dionne, C.A., Jaye, M., Rubinstein, M., Schlessinger, J. Mol. Cell. Biol. (1991) [Pubmed]
  21. Epidermal growth factor receptor-mediated cell motility: phospholipase C activity is required, but mitogen-activated protein kinase activity is not sufficient for induced cell movement. Chen, P., Xie, H., Sekar, M.C., Gupta, K., Wells, A. J. Cell Biol. (1994) [Pubmed]
  22. Tyrosines 1021 and 1009 are phosphorylation sites in the carboxy terminus of the platelet-derived growth factor receptor beta subunit and are required for binding of phospholipase C gamma and a 64-kilodalton protein, respectively. Valius, M., Bazenet, C., Kazlauskas, A. Mol. Cell. Biol. (1993) [Pubmed]
  23. The phospholipase C gamma 1-dependent pathway of Fc epsilon RI-mediated mast cell activation is regulated independently of phosphatidylinositol 3-kinase. Tkaczyk, C., Beaven, M.A., Brachman, S.M., Metcalfe, D.D., Gilfillan, A.M. J. Biol. Chem. (2003) [Pubmed]
  24. GIT1 mediates Src-dependent activation of phospholipase Cgamma by angiotensin II and epidermal growth factor. Haendeler, J., Yin, G., Hojo, Y., Saito, Y., Melaragno, M., Yan, C., Sharma, V.K., Heller, M., Aebersold, R., Berk, B.C. J. Biol. Chem. (2003) [Pubmed]
  25. CAIR-1/BAG-3 forms an EGF-regulated ternary complex with phospholipase C-gamma and Hsp70/Hsc70. Doong, H., Price, J., Kim, Y.S., Gasbarre, C., Probst, J., Liotta, L.A., Blanchette, J., Rizzo, K., Kohn, E. Oncogene (2000) [Pubmed]
  26. Engagement of the T lymphocyte antigen receptor regulates association of son-of-sevenless homologues with the SH3 domain of phospholipase Cgamma1. Scholler, J.K., Perez-Villar, J.J., O'Day, K., Kanner, S.B. Eur. J. Immunol. (2000) [Pubmed]
  27. The tyrosine phosphorylated carboxyterminus of the EGF receptor is a binding site for GAP and PLC-gamma. Margolis, B., Li, N., Koch, A., Mohammadi, M., Hurwitz, D.R., Zilberstein, A., Ullrich, A., Pawson, T., Schlessinger, J. EMBO J. (1990) [Pubmed]
  28. Oncogenic forms of the neu/HER2 tyrosine kinase are permanently coupled to phospholipase C gamma. Peles, E., Levy, R.B., Or, E., Ullrich, A., Yarden, Y. EMBO J. (1991) [Pubmed]
  29. Phospholipase C-gamma binds directly to the Na+/H+ exchanger 3 and is required for calcium regulation of exchange activity. Zachos, N.C., van Rossum, D.B., Li, X., Caraveo, G., Sarker, R., Cha, B., Mohan, S., Desiderio, S., Patterson, R.L., Donowitz, M. J. Biol. Chem. (2009) [Pubmed]
  30. Protein kinase C mu (PKC mu) associates with the B cell antigen receptor complex and regulates lymphocyte signaling. Sidorenko, S.P., Law, C.L., Klaus, S.J., Chandran, K.A., Takata, M., Kurosaki, T., Clark, E.A. Immunity (1996) [Pubmed]
  31. Structural Characterization of the Split Pleckstrin Homology Domain in Phospholipase C-{gamma}1 and Its Interaction with TRPC3. Wen, W., Yan, J., Zhang, M. J. Biol. Chem. (2006) [Pubmed]
  32. Molecular targets of CD45 in B cell antigen receptor signal transduction. Pao, L.I., Bedzyk, W.D., Persin, C., Cambier, J.C. J. Immunol. (1997) [Pubmed]
  33. TrkA glycosylation regulates receptor localization and activity. Watson, F.L., Porcionatto, M.A., Bhattacharyya, A., Stiles, C.D., Segal, R.A. J. Neurobiol. (1999) [Pubmed]
  34. Hyaluronan-CD44 interaction with Rac1-dependent protein kinase N-gamma promotes phospholipase Cgamma1 activation, Ca(2+) signaling, and cortactin-cytoskeleton function leading to keratinocyte adhesion and differentiation. Bourguignon, L.Y., Singleton, P.A., Diedrich, F. J. Biol. Chem. (2004) [Pubmed]
  35. Focal adhesion kinase-related fakB is regulated by the integrin LFA-1 and interacts with the SH3 domain of phospholipase C gamma 1. Kanner, S.B. Cell. Immunol. (1996) [Pubmed]
  36. The GTPase-activating protein of Ras suppresses platelet-derived growth factor beta receptor signaling by silencing phospholipase C-gamma 1. Valius, M., Secrist, J.P., Kazlauskas, A. Mol. Cell. Biol. (1995) [Pubmed]
  37. Ligation of the T-cell antigen receptor (TCR) induces association of hSos1, ZAP-70, phospholipase C-gamma 1, and other phosphoproteins with Grb2 and the zeta-chain of the TCR. Nel, A.E., Gupta, S., Lee, L., Ledbetter, J.A., Kanner, S.B. J. Biol. Chem. (1995) [Pubmed]
  38. Decay-accelerating factor induction on vascular endothelium by vascular endothelial growth factor (VEGF) is mediated via a VEGF receptor-2 (VEGF-R2)- and protein kinase C-alpha/epsilon (PKCalpha/epsilon)-dependent cytoprotective signaling pathway and is inhibited by cyclosporin A. Mason, J.C., Steinberg, R., Lidington, E.A., Kinderlerer, A.R., Ohba, M., Haskard, D.O. J. Biol. Chem. (2004) [Pubmed]
  39. Src homology 2 domain-containing leukocyte phosphoprotein of 76 kDa and phospholipase C gamma 1 are required for NF-kappa B activation and lipid raft recruitment of protein kinase C theta induced by T cell costimulation. Dienz, O., Möller, A., Strecker, A., Stephan, N., Krammer, P.H., Dröge, W., Schmitz, M.L. J. Immunol. (2003) [Pubmed]
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