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Gene Review

Plcg1  -  phospholipase C, gamma 1

Mus musculus

Synonyms: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1, AI894140, Cded, PLC-gamma-1, Phosphoinositide phospholipase C-gamma-1, ...
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Disease relevance of Plcg1


High impact information on Plcg1

  • Although initial studies demonstrated a role for these proteins in TCR-mediated activation of phospholipase C-gamma, recent data indicate that Tec family kinases also regulate actin cytoskeletal reorganization and cellular adhesion following TCR stimulation [6].
  • Moreover, recruitment of PLC-gamma to TrkA is essential for NGF-mediated potentiation of channel activity, and biochemical studies suggest that VR1 associates with this complex [7].
  • Platelet-derived growth factor (PDGF) stimulates phospholipase C (PLC) activity and the phosphorylation of the gamma isozyme of PLC (PLC-gamma) in vitro and in living cells [8].
  • The role of PLC-gamma in the phosphoinositide signaling pathway was addressed by examining the effect of overexpression of PLC-gamma on cellular responses to PDGF [8].
  • Effect of phospholipase C-gamma overexpression on PDGF-induced second messengers and mitogenesis [8].

Chemical compound and disease context of Plcg1


Biological context of Plcg1

  • 0. Histological analysis indicates that Plcg1 (-/-) embryos appear normal at E 8.5 but fail to continue normal development and growth beyond E 8.5-E9 [11].
  • An examination of carefully preserved wild-type embryos shows clear evidence of erythropoiesis, but erythropoiesis is not evident in Plcg1 nullizygous embryos at the same stage [12].
  • On the contrary, treatment of Plcg1(-/-) cells with PKC-specific activator increased the Bcl-2 phosphorylation, decreased caspase-3 activity and improved their survival [13].
  • Plcg2 does not map near its most closely related family member, Plcg1, in either genome, indicating that the mammalian Plcg genes belong to a dispersed family [14].
  • By contrast, a receptor mutated in both the PI3K and PLC gamma association sites can still stimulate mast cell growth, indicating a crucial role of these effector molecules in regulating adhesion rather than cell growth [15].

Anatomical context of Plcg1

  • Epidermal growth factor signaling and mitogenesis in Plcg1 null mouse embryonic fibroblasts [16].
  • However, non-erythroid granulocyte/macrophage colonies are produced by Plcg1 null embryos [12].
  • Activation of PKC was also markedly increased in both cell lines treated with H(2)O(2) (1-5 mM), but with low doses (50-200 microM), PKC activation was considerably decreased in Plcg1(-/-) cells [13].
  • Kit signaling inhibits the sphingomyelin-ceramide pathway through PLC gamma 1: implication in stem cell factor radioprotective effect [17].
  • In contrast, PLC alpha and PLC gamma 2 were abundantly expressed in all B cell lines tested [18].

Associations of Plcg1 with chemical compounds

  • Our findings establish the significance of PLC gamma affinity for signal definition, the role of this receptor tyrosine kinase substrate as a negative feedback regulator and the importance of this regulatory function for mitogenesis and its disturbance in oncogenic aberrations [19].
  • Relative to wild-type EGFR, the PLC gamma affinity increase of the EGFR switch mutant EGFR.X enhanced its inositol trisphosphate (IP3) and calcium signals and resulted in a more sustained mitogen-activated protein (MAP) kinase activation and accelerated receptor dephosphorylation [19].
  • Specifically, 4 CRUs of AHNAK bind and activate PKC-alpha, which in turn stimulates the release of arachidonic acid near where PLC-gamma1 is localized [20].
  • Integrin-dependent PLC-gamma1 phosphorylation mediates fibronectin-dependent adhesion [21].
  • The soluble tyrosine kinase inhibitors, genistein (100 microM), herbimycin (10 microM) and geldanamycin (0.6 microM) which could affect signalling through PLC gamma hindered but never completely inhibited Ca2+ spiking in response to fertilization [22].

Physical interactions of Plcg1


Enzymatic interactions of Plcg1


Regulatory relationships of Plcg1


Other interactions of Plcg1


Analytical, diagnostic and therapeutic context of Plcg1


  1. Calcium-sensing receptor-mediated activation of phospholipase C-gamma1 is downstream of phospholipase C-beta and protein kinase C in MC3T3-E1 osteoblasts. Godwin, S.L., Soltoff, S.P. Bone (2002) [Pubmed]
  2. Deficiency of phospholipase C-gamma1 impairs renal development and hematopoiesis. Shirane, M., Sawa, H., Kobayashi, Y., Nakano, T., Kitajima, K., Shinkai, Y., Nagashima, K., Negishi, I. Development (2001) [Pubmed]
  3. Two species of mRNAs for the fyn proto-oncogene are produced by an alternative polyadenylation. Lee, C., Kim, M.G., Jeon, S.H., Park, D.E., Park, S.D., Seong, R.H. Mol. Cells (1998) [Pubmed]
  4. Activity of the epidermal-growth-factor receptor and phospholipase C-gamma 1 in heat-stressed fibroblasts and A-431 cells. Liu, S.M., Carpenter, G. Biochem. J. (1992) [Pubmed]
  5. Phospholipase C-gamma 1 can induce DNA synthesis by a mechanism independent of its lipase activity. Smith, M.R., Liu, Y.L., Matthews, N.T., Rhee, S.G., Sung, W.K., Kung, H.F. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  6. Tec family kinases in T lymphocyte development and function. Berg, L.J., Finkelstein, L.D., Lucas, J.A., Schwartzberg, P.L. Annu. Rev. Immunol. (2005) [Pubmed]
  7. Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition. Chuang , H.H., Prescott, E.D., Kong, H., Shields, S., Jordt, S.E., Basbaum, A.I., Chao, M.V., Julius, D. Nature (2001) [Pubmed]
  8. Effect of phospholipase C-gamma overexpression on PDGF-induced second messengers and mitogenesis. Margolis, B., Zilberstein, A., Franks, C., Felder, S., Kremer, S., Ullrich, A., Rhee, S.G., Skorecki, K., Schlessinger, J. Science (1990) [Pubmed]
  9. Reduced expression of PLC-gamma during the differentiation of mouse F9 teratocarcinoma cells. Lee, Y.H., Lee, H.Y., Ryu, S.H., Suh, P.G., Kim, K.W. Cancer Lett. (1993) [Pubmed]
  10. Inhibition of PDGF-induced phosphoinositide-turnover by glucopiericidin A. Ahn, S.C., Kim, B.Y., Park, C.S., Lee, H.S., Suh, P.G., Ryu, S.H., Rho, H.M., Rhee, J.S., Mheen, T.I., Ahn, J.S. Biochem. Mol. Biol. Int. (1995) [Pubmed]
  11. Essential role of the tyrosine kinase substrate phospholipase C-gamma1 in mammalian growth and development. Ji, Q.S., Winnier, G.E., Niswender, K.D., Horstman, D., Wisdom, R., Magnuson, M.A., Carpenter, G. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  12. Absence of erythrogenesis and vasculogenesis in Plcg1-deficient mice. Liao, H.J., Kume, T., McKay, C., Xu, M.J., Ihle, J.N., Carpenter, G. J. Biol. Chem. (2002) [Pubmed]
  13. Phospholipase C-gamma1 is required for cell survival in oxidative stress by protein kinase C. Bai, X.C., Deng, F., Liu, A.L., Zou, Z.P., Wang, Y., Ke, Z.Y., Ji, Q.S., Luo, S.Q. Biochem. J. (2002) [Pubmed]
  14. Phospholipase C gamma-2 (Plcg2) and phospholipase C gamma-1 (Plcg1) map to distinct regions in the human and mouse genomes. Argeson, A.C., Druck, T., Veronese, M.L., Knopf, J.L., Buchberg, A.M., Huebner, K., Siracusa, L.D. Genomics (1995) [Pubmed]
  15. Receptor tyrosine kinase stimulates cell-matrix adhesion by phosphatidylinositol 3 kinase and phospholipase C-gamma 1 pathways. Kinashi, T., Escobedo, J.A., Williams, L.T., Takatsu, K., Springer, T.A. Blood (1995) [Pubmed]
  16. Epidermal growth factor signaling and mitogenesis in Plcg1 null mouse embryonic fibroblasts. Ji, Q.S., Ermini, S., Baulida, J., Sun, F.L., Carpenter, G. Mol. Biol. Cell (1998) [Pubmed]
  17. Kit signaling inhibits the sphingomyelin-ceramide pathway through PLC gamma 1: implication in stem cell factor radioprotective effect. Maddens, S., Charruyer, A., Plo, I., Dubreuil, P., Berger, S., Salles, B., Laurent, G., Jaffrézou, J.P. Blood (2002) [Pubmed]
  18. Expression of phospholipase C isozymes by murine B lymphocytes. Hempel, W.M., DeFranco, A.L. J. Immunol. (1991) [Pubmed]
  19. Transforming potentials of epidermal growth factor and nerve growth factor receptors inversely correlate with their phospholipase C gamma affinity and signal activation. Obermeier, A., Tinhofer, I., Grunicke, H.H., Ullrich, A. EMBO J. (1996) [Pubmed]
  20. AHNAK-mediated activation of phospholipase C-gamma1 through protein kinase C. Lee, I.H., You, J.O., Ha, K.S., Bae, D.S., Suh, P.G., Rhee, S.G., Bae, Y.S. J. Biol. Chem. (2004) [Pubmed]
  21. Integrin-dependent PLC-gamma1 phosphorylation mediates fibronectin-dependent adhesion. Tvorogov, D., Wang, X.J., Zent, R., Carpenter, G. J. Cell. Sci. (2005) [Pubmed]
  22. Phospholipase C in mouse oocytes: characterization of beta and gamma isoforms and their possible involvement in sperm-induced Ca2+ spiking. Dupont, G., McGuinness, O.M., Johnson, M.H., Berridge, M.J., Borgese, F. Biochem. J. (1996) [Pubmed]
  23. Tumorigenesis mediated by MET mutant M1268T is inhibited by dominant-negative Src. Nakaigawa, N., Weirich, G., Schmidt, L., Zbar, B. Oncogene (2000) [Pubmed]
  24. Identification of the major sites of autophosphorylation of the murine protein-tyrosine kinase Syk. Furlong, M.T., Mahrenholz, A.M., Kim, K.H., Ashendel, C.L., Harrison, M.L., Geahlen, R.L. Biochim. Biophys. Acta (1997) [Pubmed]
  25. Growth factor-induced binding of dynamin to signal transduction proteins involves sorting to distinct and separate proline-rich dynamin sequences. Scaife, R., Gout, I., Waterfield, M.D., Margolis, R.L. EMBO J. (1994) [Pubmed]
  26. Activation of mouse sperm phosphatidylinositol-4,5 bisphosphate-phospholipase C by zona pellucida is modulated by tyrosine phosphorylation. Tomes, C.N., McMaster, C.R., Saling, P.M. Mol. Reprod. Dev. (1996) [Pubmed]
  27. Proteolytic cleavage of phospholipase C-gamma1 during apoptosis in Molt-4 cells. Bae, S.S., Perry, D.K., Oh, Y.S., Choi, J.H., Galadari, S.H., Ghayur, T., Ryu, S.H., Hannun, Y.A., Suh, P.G. FASEB J. (2000) [Pubmed]
  28. Platelet-derived growth factor (PDGF)-dependent association of phospholipase C-gamma with the PDGF receptor signaling complex. Morrison, D.K., Kaplan, D.R., Rhee, S.G., Williams, L.T. Mol. Cell. Biol. (1990) [Pubmed]
  29. Specific changes of Ras GTPase-activating protein (GAP) and a GAP-associated p62 protein during calcium-induced keratinocyte differentiation. Filvaroff, E., Calautti, E., McCormick, F., Dotto, G.P. Mol. Cell. Biol. (1992) [Pubmed]
  30. Signal transduction by normal isoforms and W mutant variants of the Kit receptor tyrosine kinase. Reith, A.D., Ellis, C., Lyman, S.D., Anderson, D.M., Williams, D.E., Bernstein, A., Pawson, T. EMBO J. (1991) [Pubmed]
  31. The PLC-PKC cascade is required for IL-1beta-dependent Erk and Akt activation: their role in proliferation. Amin, A.R., Ichigotani, Y., Oo, M.L., Biswas, M.H., Yuan, H., Huang, P., Mon, N.N., Hamaguchi, M. Int. J. Oncol. (2003) [Pubmed]
  32. Macrophage/microglia-specific protein Iba1 enhances membrane ruffling and Rac activation via phospholipase C-gamma -dependent pathway. Kanazawa, H., Ohsawa, K., Sasaki, Y., Kohsaka, S., Imai, Y. J. Biol. Chem. (2002) [Pubmed]
  33. Activation of phospholipase C induces the expression of the multidrug resistance (MDR1) gene through the Raf-MAPK pathway. Yang, J.M., Vassil, A.D., Hait, W.N. Mol. Pharmacol. (2001) [Pubmed]
  34. PLC-gamma1 is required for IGF-I protection from cell death induced by loss of extracellular matrix adhesion. Chattopadhyay, A., Carpenter, G. J. Cell. Sci. (2002) [Pubmed]
  35. Phospholipase C-gamma, protein kinase C and Ca2+/calmodulin-dependent protein kinase II are involved in platelet-derived growth factor-induced phosphorylation of Tiam1. Fleming, I.N., Elliott, C.M., Exton, J.H. FEBS Lett. (1998) [Pubmed]
  36. Cytoplasmic and nuclear phospholipase C-beta 1 relocation: role in resumption of meiosis in the mouse oocyte. Avazeri, N., Courtot, A.M., Pesty, A., Duquenne, C., Lefèvre, B. Mol. Biol. Cell (2000) [Pubmed]
  37. Angiotensin II stimulates tyrosine phosphorylation of phospholipase C-gamma-associated proteins. Characterization of a c-Src-dependent 97-kD protein in vascular smooth muscle cells. Schmitz, U., Ishida, M., Berk, B.C. Circ. Res. (1997) [Pubmed]
  38. Steel factor-induced tyrosine phosphorylation in murine mast cells. Common elements with IL-3-induced signal transduction pathways. Welham, M.J., Schrader, J.W. J. Immunol. (1992) [Pubmed]
  39. Interaction of elongation factor-1alpha and pleckstrin homology domain of phospholipase C-gamma 1 with activating its activity. Chang, J.S., Seok, H., Kwon, T.K., Min, d.o. .S., Ahn, B.H., Lee, Y.H., Suh, J.W., Kim, J.W., Iwashita, S., Omori, A., Ichinose, S., Numata, O., Seo, J.K., Oh, Y.S., Suh, P.G. J. Biol. Chem. (2002) [Pubmed]
  40. Trophoblast adhesion of the peri-implantation mouse blastocyst is regulated by integrin signaling that targets phospholipase C. Wang, J., Mayernik, L., Armant, D.R. Dev. Biol. (2007) [Pubmed]
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