PLCG2 explained

1-Phosphatidylinositol-4,5-bisphosphate phosphodiesterase gamma-2 is an enzyme that in humans is encoded by the PLCG2 gene.^{[1] [2]}

Function

From OMIM as of March 24, 2020:^[3]

Enzymes of the phospholipase C family catalyze the hydrolysis of phospholipids to yield diacylglycerols and water-soluble phosphorylated derivatives of the lipid head groups. A number of these enzymes have specificity for phosphoinositides. Of the phosphoinositide-specific phospholipase C enzymes, C-beta is regulated by heterotrimeric G protein-coupled receptors, while the closely related C-gamma-1 (PLCG1; MIM 172420) and C-gamma-2 enzymes are controlled by receptor tyrosine kinases. The C-gamma-1 and C-gamma-2 enzymes are composed of phospholipase domains that flank regions of homology to noncatalytic domains of the SRC oncogene product, SH2 and SH3.

Interactions

PLCG2 has been shown to interact with:

• Bruton's tyrosine kinase,^[4]
• GAB2,
• LYN,^{[5] [6]}
• PTPN11,^[7] and
• SHC1^{[7] [8]}

References

Further reading

• Fruman DA, Satterthwaite AB, Witte ON . Xid-like phenotypes: a B cell signalosome takes shape . Immunity . 13 . 1 . 1–3 . 2000 . 10933389 . 10.1016/S1074-7613(00)00002-9 . free .
• Cefai D, Debre P, Kaczorek M, Idziorek T, Autran B, Bismuth G . Human immunodeficiency virus-1 glycoproteins gp120 and gp160 specifically inhibit the CD3/T cell-antigen receptor phosphoinositide transduction pathway . J. Clin. Invest. . 86 . 6 . 2117–24 . 1990 . 1979339 . 329852 . 10.1172/JCI114950 .
• Ohta S, Matsui A, Nazawa Y, Kagawa Y . Complete cDNA encoding a putative phospholipase C from transformed human lymphocytes . FEBS Lett. . 242 . 1 . 31–5 . 1988 . 2849563 . 10.1016/0014-5793(88)80979-7 . 20986590 . free .
• Yan W, Ratnam M . Preferred sites of glycosylphosphatidylinositol modification in folate receptors and constraints in the primary structure of the hydrophobic portion of the signal . Biochemistry . 34 . 44 . 14594–600 . 1995 . 7578066 . 10.1021/bi00044a039 .
• Zauli G, Previati M, Caramelli E, Bassini A, Falcieri E, Gibellini D, Bertolaso L, Bosco D, Robuffo I, Capitani S . Exogenous human immunodeficiency virus type-1 Tat protein selectively stimulates a phosphatidylinositol-specific phospholipase C nuclear pathway in the Jurkat T cell line . Eur. J. Immunol. . 25 . 9 . 2695–700 . 1995 . 7589147 . 10.1002/eji.1830250944 . 20562627 .
• Liao F, Shin HS, Rhee SG . In vitro tyrosine phosphorylation of PLC-gamma 1 & PLC-gamma 2 by src-family protein tyrosine kinases . Biochem. Biophys. Res. Commun. . 191 . 3 . 1028–1033 . 1993 . 7682059 . 10.1006/bbrc.1993.1320 . 298050 .
• Daniel JL, Dangelmaier C, Smith JB . Evidence for a role for tyrosine phosphorylation of phospholipase C gamma 2 in collagen-induced platelet cytosolic calcium mobilization . Biochem. J. . 302 . 2 . 617–22 . 1994 . 8093016 . 1137272 . 10.1042/bj3020617.
• Obermeier A, Lammers R, Wiesmüller KH, Jung G, Schlessinger J, Ullrich A . Identification of Trk binding sites for SHC and phosphatidylinositol 3'-kinase and formation of a multimeric signaling complex . J. Biol. Chem. . 268 . 31 . 22963–6 . 1993 . 10.1016/S0021-9258(19)49410-6 . 8226808 . free .
• Pleiman CM, Clark MR, Gauen LK, Winitz S, Coggeshall KM, Johnson GL, Shaw AS, Cambier JC . Mapping of sites on the Src family protein tyrosine kinases p55blk, p59fyn, and p56lyn which interact with the effector molecules phospholipase C-gamma 2, microtubule-associated protein kinase, GTPase-activating protein, and phosphatidylinositol 3-kinase . Mol. Cell. Biol. . 13 . 9 . 5877–87 . 1993 . 8395016 . 360336 . 10.1128/MCB.13.9.5877.
• Sidorenko SP, Law CL, Klaus SJ, Chandran KA, Takata M, Kurosaki T, Clark EA . Protein kinase C mu (PKC mu) associates with the B cell antigen receptor complex and regulates lymphocyte signaling . Immunity . 5 . 4 . 353–63 . 1996 . 8885868 . 10.1016/S1074-7613(00)80261-7 . free .
• Kang JS, Kohlhuber F, Hug H, Marmé D, Eick D, Ueffing M . Cloning and functional analysis of the hematopoietic cell-specific phospholipase C(gamma)2 promoter . FEBS Lett. . 399 . 1–2 . 14–20 . 1996 . 8980110 . 10.1016/S0014-5793(96)01276-8 . 85872860 .
• Chen P, Mayne M, Power C, Nath A . The Tat protein of HIV-1 induces tumor necrosis factor-alpha production. Implications for HIV-1-associated neurological diseases . J. Biol. Chem. . 272 . 36 . 22385–8 . 1997 . 9278385 . 10.1074/jbc.272.36.22385 . free .
• Cunningham SA, Arrate MP, Brock TA, Waxham MN . Interactions of FLT-1 and KDR with phospholipase C gamma: identification of the phosphotyrosine binding sites . Biochem. Biophys. Res. Commun. . 240 . 3 . 635–9 . 1997 . 9398617 . 10.1006/bbrc.1997.7719 .
• Mayne M, Bratanich AC, Chen P, Rana F, Nath A, Power C . HIV-1 tat molecular diversity and induction of TNF-alpha: implications for HIV-induced neurological disease . Neuroimmunomodulation . 5 . 3–4 . 184–92 . 1998 . 9730685 . 10.1159/000026336 . 19529677 .
• Bai RY, Dieter P, Peschel C, Morris SW, Duyster J . Nucleophosmin-anaplastic lymphoma kinase of large-cell anaplastic lymphoma is a constitutively active tyrosine kinase that utilizes phospholipase C-gamma to mediate its mitogenicity . Mol. Cell. Biol. . 18 . 12 . 6951–61 . 1998 . 9819383 . 109278 . 10.1128/mcb.18.12.6951.
• Tomassetti A, Bottero F, Mazzi M, Miotti S, Colnaghi MI, Canevari S . Molecular requirements for attachment of the glycosylphosphatidylinositol anchor to the human alpha folate receptor . J. Cell. Biochem. . 72 . 1 . 111–8 . 1999 . 10025672 . 10.1002/(SICI)1097-4644(19990101)72:1<111::AID-JCB12>3.0.CO;2-1 . 23174724 .
• Shen Z, Batzer A, Koehler JA, Polakis P, Schlessinger J, Lydon NB, Moran MF . Evidence for SH3 domain directed binding and phosphorylation of Sam68 by Src . Oncogene . 18 . 33 . 4647–53 . 1999 . 10467411 . 10.1038/sj.onc.1203079 . 19801963 .
• Gross BS, Melford SK, Watson SP . Evidence that phospholipase C-gamma2 interacts with SLP-76, Syk, Lyn, LAT and the Fc receptor gamma-chain after stimulation of the collagen receptor glycoprotein VI in human platelets . Eur. J. Biochem. . 263 . 3 . 612–23 . 1999 . 10469124 . 10.1046/j.1432-1327.1999.00560.x . free .
• Haughey NJ, Holden CP, Nath A, Geiger JD . Involvement of inositol 1,4,5-trisphosphate-regulated stores of intracellular calcium in calcium dysregulation and neuron cell death caused by HIV-1 protein tat . J. Neurochem. . 73 . 4 . 1363–74 . 1999 . 10501179 . 10.1046/j.1471-4159.1999.0731363.x . 25410140 .

Notes and References

1. Hernandez D, Egan SE, Yulug IG, Fisher EM . Mapping the gene that encodes phosphatidylinositol-specific phospholipase C-gamma 2 in the human and the mouse . Genomics . 23 . 2 . 504–7 . February 1995 . 7835906 . 10.1006/geno.1994.1533 .
2. Web site: Entrez Gene: PLCG2 phospholipase C, gamma 2 (phosphatidylinositol-specific).
3. Web site: 600220: PHOSPHOLIPASE C, GAMMA-2; PLCG2 . Bocchini . Carol A. . 2020-03-24 . . Johns Hopkins University . en . 2023-01-29.
4. Yasuda T, Tezuka T, Maeda A, Inazu T, Yamanashi Y, Gu H, Kurosaki T, Yamamoto T . Cbl-b positively regulates Btk-mediated activation of phospholipase C-gamma2 in B cells . J. Exp. Med. . 196 . 1 . 51–63 . July 2002 . 12093870 . 2194016 . 10.1084/jem.20020068.
5. Guo B, Kato RM, Garcia-Lloret M, Wahl MI, Rawlings DJ . Engagement of the human pre-B cell receptor generates a lipid raft-dependent calcium signaling complex . Immunity . 13 . 2 . 243–53 . August 2000 . 10981967 . 10.1016/s1074-7613(00)00024-8. free .
6. Pleiman CM, Clark MR, Gauen LK, Winitz S, Coggeshall KM, Johnson GL, Shaw AS, Cambier JC . Mapping of sites on the Src family protein tyrosine kinases p55blk, p59fyn, and p56lyn which interact with the effector molecules phospholipase C-gamma 2, microtubule-associated protein kinase, GTPase-activating protein, and phosphatidylinositol 3-kinase . Mol. Cell. Biol. . 13 . 9 . 5877–87 . September 1993 . 8395016 . 360336 . 10.1128/MCB.13.9.5877.
7. Boudot C, Kadri Z, Petitfrère E, Lambert E, Chrétien S, Mayeux P, Haye B, Billat C . Phosphatidylinositol 3-kinase regulates glycosylphosphatidylinositol hydrolysis through PLC-gamma(2) activation in erythropoietin-stimulated cells . Cell. Signal. . 14 . 10 . 869–78 . October 2002 . 12135708 . 10.1016/s0898-6568(02)00036-0.
8. Perskvist N, Zheng L, Stendahl O . Activation of human neutrophils by Mycobacterium tuberculosis H37Ra involves phospholipase C gamma 2, Shc adapter protein, and p38 mitogen-activated protein kinase . J. Immunol. . 164 . 2 . 959–65 . January 2000 . 10623845 . 10.4049/jimmunol.164.2.959. 19134463 .