PLCG1

From Wikipedia, the free encyclopedia
Phospholipase C, gamma 1

PDB rendering based on 1hsq.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
SymbolsPLCG1; NCKAP3; PLC-II; PLC1; PLC148; PLCgamma1
External IDsOMIM: 172420 MGI: 97615 HomoloGene: 1997 ChEMBL: 3964 GeneCards: PLCG1 Gene
EC number3.1.4.11
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez533518803
EnsemblENSG00000124181ENSMUSG00000016933
UniProtP19174Q62077
RefSeq (mRNA)NM_002660NM_021280
RefSeq (protein)NP_002651NP_067255
Location (UCSC)Chr 20:
39.77 – 39.83 Mb		Chr 2:
160.73 – 160.78 Mb
PubMed search
This box:

Phospholipase C, gamma 1, also known as PLCG1, is a protein that in humans is encoded by the PLCG1 gene.[1][2]

Function

The protein encoded by this gene catalyzes the formation of inositol 1,4,5-trisphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate. This reaction uses calcium as a cofactor and plays an important role in the intracellular transduction of receptor-mediated tyrosine kinase activators. For example, when activated by SRC, the encoded protein causes the Ras guanine nucleotide exchange factor RASGRP1 to translocate to the Golgi apparatus, where it activates Ras. Also, this protein has been shown to be a major substrate for heparin-binding growth factor 1 (acidic fibroblast growth factor)-activated tyrosine kinase. The receptor protein tyrosine phosphatase PTPmu (PTPRM) is capable of dephosphorylating PLCG1.[3] Two transcript variants encoding different isoforms have been found for this gene.[4]

Clinical significance

Researchers studying PLCg1 and its role in breast cancer metastasis discovered this gene can promote cancer metastasis and subsequently blocking it stopped cancer from spreading. Research is ongoing but this gene could lead to the development of new anti-cancer drugs.[5][6]

Interactions

PLCG1 has been shown to interact with:

See also


References

  1. ↑ Bristol A, Hall SM, Kriz RW, Stahl ML, Fan YS, Byers MG, Eddy RL, Shows TB, Knopf JL (1988). "Phospholipase C-148: chromosomal location and deletion mapping of functional domains". Cold Spring Harb. Symp. Quant. Biol. 53 Pt 2: 915–20. PMID 3254788. 
  2. ↑ Burgess WH, Dionne CA, Kaplow J, Mudd R, Friesel R, Zilberstein A, Schlessinger J, Jaye M (September 1990). "Characterization and cDNA cloning of phospholipase C-gamma, a major substrate for heparin-binding growth factor 1 (acidic fibroblast growth factor)-activated tyrosine kinase". Mol. Cell. Biol. 10 (9): 4770–7. PMC 361079. PMID 2167438. 
  3. ↑ 3.0 3.1 Phillips-Mason PJ, Kaur H, Burden-Gulley SM, Craig SE, Brady-Kalnay SM (2011). "Identification of phospholipase C gamma1 as a protein tyrosine phosphatase mu substrate that regulates cell migration.". J Cell Biochem 112 (1): 39–48. doi:10.1002/jcb.22710. PMC 3031780. PMID 20506511. 
  4. ↑ "Entrez Gene: PLCG1 phospholipase C, gamma 1". 
  5. ↑ Smith R (2008-12-14). "Scientists may be able to stop cancer spreading round the body". Health News. Telegraph.co.uk. Retrieved 2008-12-17. 
  6. ↑ Sala G, Dituri F, Raimondi C, Previdi S, Maffucci T, Mazzoletti M, Rossi C, Iezzi M, Lattanzio R, Piantelli M, Iacobelli S, Broggini M, Falasca M (December 2008). "Phospholipase C{gamma}1 Is Required for Metastasis Development and Progression". Cancer Res. 68 (24): 10187–96. doi:10.1158/0008-5472.CAN-08-1181. PMID 19074886. 
  7. ↑ Oneyama, Chitose; Nakano Hirofumi, Sharma Sreenath V (March 2002). "UCS15A, a novel small molecule, SH3 domain-mediated protein-protein interaction blocking drug". Oncogene (England) 21 (13): 2037–50. doi:10.1038/sj.onc.1205271. ISSN 0950-9232. PMID 11960376. 
  8. ↑ Jabado, N; Jauliac S, Pallier A, Bernard F, Fischer A, Hivroz C (September 1998). "Sam68 association with p120GAP in CD4+ T cells is dependent on CD4 molecule expression". J. Immunol. (UNITED STATES) 161 (6): 2798–803. ISSN 0022-1767. PMID 9743338. 
  9. ↑ Shen, Z; Batzer A, Koehler J A, Polakis P, Schlessinger J, Lydon N B, Moran M F (August 1999). "Evidence for SH3 domain directed binding and phosphorylation of Sam68 by Src". Oncogene (ENGLAND) 18 (33): 4647–53. doi:10.1038/sj.onc.1203079. ISSN 0950-9232. PMID 10467411. 
  10. ↑ Ohmichi, M; Decker S J, Pang L, Saltiel A R (August 1991). "Nerve growth factor binds to the 140 kd trk proto-oncogene product and stimulates its association with the src homology domain of phospholipase C gamma 1". Biochem. Biophys. Res. Commun. (UNITED STATES) 179 (1): 217–23. doi:10.1016/0006-291X(91)91357-I. ISSN 0006-291X. PMID 1715690. 
  11. ↑ Qian, X; Riccio A, Zhang Y, Ginty D D (November 1998). "Identification and characterization of novel substrates of Trk receptors in developing neurons". Neuron (UNITED STATES) 21 (5): 1017–29. doi:10.1016/S0896-6273(00)80620-0. ISSN 0896-6273. PMID 9856458. 
  12. ↑ 12.0 12.1 Meakin, S O; MacDonald J I, Gryz E A, Kubu C J, Verdi J M (April 1999). "The signaling adapter FRS-2 competes with Shc for binding to the nerve growth factor receptor TrkA. A model for discriminating proliferation and differentiation". J. Biol. Chem. (UNITED STATES) 274 (14): 9861–70. doi:10.1074/jbc.274.14.9861. ISSN 0021-9258. PMID 10092678. 
  13. ↑ Koch, A; Mancini A, Stefan M, Niedenthal R, Niemann H, Tamura T (March 2000). "Direct interaction of nerve growth factor receptor, TrkA, with non-receptor tyrosine kinase, c-Abl, through the activation loop". FEBS Lett. (NETHERLANDS) 469 (1): 72–6. doi:10.1016/S0014-5793(00)01242-4. ISSN 0014-5793. PMID 10708759. 
  14. ↑ Doong, H; Price J, Kim Y S, Gasbarre C, Probst J, Liotta L A, Blanchette J, Rizzo K, Kohn E (September 2000). "CAIR-1/BAG-3 forms an EGF-regulated ternary complex with phospholipase C-gamma and Hsp70/Hsc70". Oncogene (ENGLAND) 19 (38): 4385–95. doi:10.1038/sj.onc.1203797. ISSN 0950-9232. PMID 10980614. 
  15. ↑ Yablonski, D; Kadlecek T, Weiss A (July 2001). "Identification of a phospholipase C-gamma1 (PLC-gamma1) SH3 domain-binding site in SLP-76 required for T-cell receptor-mediated activation of PLC-gamma1 and NFAT". Mol. Cell. Biol. (United States) 21 (13): 4208–18. doi:10.1128/MCB.21.13.4208-4218.2001. ISSN 0270-7306. PMC 87082. PMID 11390650. 
  16. ↑ Thodeti, Charles Kumar; Massoumi Ramin, Bindslev Lene, Sjölander Anita (July 2002). "Leukotriene D4 induces association of active RhoA with phospholipase C-gamma1 in intestinal epithelial cells". Biochem. J. (England) 365 (Pt 1): 157–63. doi:10.1042/BJ20020248. ISSN 0264-6021. PMC 1222665. PMID 12071848. 
  17. ↑ van Dijk, T B; van Den Akker E, Amelsvoort M P, Mano H, Löwenberg B, von Lindern M (November 2000). "Stem cell factor induces phosphatidylinositol 3'-kinase-dependent Lyn/Tec/Dok-1 complex formation in hematopoietic cells". Blood (UNITED STATES) 96 (10): 3406–13. ISSN 0006-4971. PMID 11071635. 
  18. ↑ Jhun, B H; Rivnay B, Price D, Avraham H (April 1995). "The MATK tyrosine kinase interacts in a specific and SH2-dependent manner with c-Kit". J. Biol. Chem. (UNITED STATES) 270 (16): 9661–6. doi:10.1074/jbc.270.16.9661. ISSN 0021-9258. PMID 7536744. 
  19. ↑ Pumphrey, N J; Taylor V, Freeman S, Douglas M R, Bradfield P F, Young S P, Lord J M, Wakelam M J, Bird I N, Salmon M, Buckley C D (April 1999). "Differential association of cytoplasmic signalling molecules SHP-1, SHP-2, SHIP and phospholipase C-gamma1 with PECAM-1/CD31". FEBS Lett. (NETHERLANDS) 450 (1-2): 77–83. doi:10.1016/S0014-5793(99)00446-9. ISSN 0014-5793. PMID 10350061. 
  20. ↑ Perez-Villar, J J; Kanner S B (December 1999). "Regulated association between the tyrosine kinase Emt/Itk/Tsk and phospholipase-C gamma 1 in human T lymphocytes". J. Immunol. (UNITED STATES) 163 (12): 6435–41. ISSN 0022-1767. PMID 10586033. 
  21. ↑ Hao, Shengli; August Avery (August 2002). "The proline rich region of the Tec homology domain of ITK regulates its activity". FEBS Lett. (Netherlands) 525 (1-3): 53–8. doi:10.1016/S0014-5793(02)03066-1. ISSN 0014-5793. PMID 12163161. 
  22. ↑ Jang, Il Ho; Lee Sukmook, Park Jong Bae, Kim Jong Hyun, Lee Chang Sup, Hur Eun-Mi, Kim Il Shin, Kim Kyong-Tai, Yagisawa Hitoshi, Suh Pann-Ghill, Ryu Sung Ho (May 2003). "The direct interaction of phospholipase C-gamma 1 with phospholipase D2 is important for epidermal growth factor signaling". J. Biol. Chem. (United States) 278 (20): 18184–90. doi:10.1074/jbc.M208438200. ISSN 0021-9258. PMID 12646582. 
  23. ↑ Haendeler, Judith; Yin Guoyong, Hojo Yukihiro, Saito Yuji, Melaragno Matthew, Yan Chen, Sharma Virendra K, Heller Manfred, Aebersold Ruedi, Berk Bradford C (December 2003). "GIT1 mediates Src-dependent activation of phospholipase Cgamma by angiotensin II and epidermal growth factor". J. Biol. Chem. (United States) 278 (50): 49936–44. doi:10.1074/jbc.M307317200. ISSN 0021-9258. PMID 14523024. 
  24. ↑ Ueno, E; Haruta T, Uno T, Usui I, Iwata M, Takano A, Kawahara J, Sasaoka T, Ishibashi O, Kobayashi M (July 2001). "Potential role of Gab1 and phospholipase C-gamma in osmotic shock-induced glucose uptake in 3T3-L1 adipocytes". Horm. Metab. Res. (Germany) 33 (7): 402–6. doi:10.1055/s-2001-16227. ISSN 0018-5043. PMID 11507676. 
  25. ↑ Holgado-Madruga, M; Emlet D R, Moscatello D K, Godwin A K, Wong A J (February 1996). "A Grb2-associated docking protein in EGF- and insulin-receptor signalling". Nature (ENGLAND) 379 (6565): 560–4. doi:10.1038/379560a0. ISSN 0028-0836. PMID 8596638. 
  26. ↑ Kapeller, R; Moriarty A, Strauss A, Stubdal H, Theriault K, Siebert E, Chickering T, Morgenstern J P, Tartaglia L A, Lillie J (August 1999). "Tyrosine phosphorylation of tub and its association with Src homology 2 domain-containing proteins implicate tub in intracellular signaling by insulin". J. Biol. Chem. (UNITED STATES) 274 (35): 24980–6. doi:10.1074/jbc.274.35.24980. ISSN 0021-9258. PMID 10455176. 
  27. ↑ Cunningham, S A; Arrate M P, Brock T A, Waxham M N (November 1997). "Interactions of FLT-1 and KDR with phospholipase C gamma: identification of the phosphotyrosine binding sites". Biochem. Biophys. Res. Commun. (UNITED STATES) 240 (3): 635–9. doi:10.1006/bbrc.1997.7719. ISSN 0006-291X. PMID 9398617. 
  28. ↑ Pei, Z; Maloney J A, Yang L, Williamson J R (September 1997). "A new function for phospholipase C-gamma1: coupling to the adaptor protein GRB2". Arch. Biochem. Biophys. (UNITED STATES) 345 (1): 103–10. doi:10.1006/abbi.1997.0245. ISSN 0003-9861. PMID 9281317. 
  29. ↑ Nel, A E; Gupta S, Lee L, Ledbetter J A, Kanner S B (August 1995). "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". J. Biol. Chem. (UNITED STATES) 270 (31): 18428–36. doi:10.1074/jbc.270.31.18428. ISSN 0021-9258. PMID 7629168. 
  30. ↑ 30.0 30.1 Scholler, J K; Perez-Villar J J, O'Day K, Kanner S B (August 2000). "Engagement of the T lymphocyte antigen receptor regulates association of son-of-sevenless homologues with the SH3 domain of phospholipase Cgamma1". Eur. J. Immunol. (GERMANY) 30 (8): 2378–87. doi:10.1002/1521-4141(2000)30:8<2378::AID-IMMU2378>3.0.CO;2-E. ISSN 0014-2980. PMID 10940929. 
  31. ↑ Sozzani, P; Hasan L, Séguélas M H, Caput D, Ferrara P, Pipy B, Cambon C (March 1998). "IL-13 induces tyrosine phosphorylation of phospholipase C gamma-1 following IRS-2 association in human monocytes: relationship with the inhibitory effect of IL-13 on ROI production". Biochem. Biophys. Res. Commun. (UNITED STATES) 244 (3): 665–70. doi:10.1006/bbrc.1998.8314. ISSN 0006-291X. PMID 9535722. 
  32. ↑ Bertagnolo, V; Marchisio M, Volinia S, Caramelli E, Capitani S (December 1998). "Nuclear association of tyrosine-phosphorylated Vav to phospholipase C-gamma1 and phosphoinositide 3-kinase during granulocytic differentiation of HL-60 cells". FEBS Lett. (NETHERLANDS) 441 (3): 480–4. doi:10.1016/S0014-5793(98)01593-2. ISSN 0014-5793. PMID 9891995. 
  33. ↑ Peles, E; Levy R B, Or E, Ullrich A, Yarden Y (August 1991). "Oncogenic forms of the neu/HER2 tyrosine kinase are permanently coupled to phospholipase C gamma". EMBO J. (ENGLAND) 10 (8): 2077–86. ISSN 0261-4189. PMC 452891. PMID 1676673. 
  34. ↑ Arteaga, C L; Johnson M D, Todderud G, Coffey R J, Carpenter G, Page D L (December 1991). "Elevated content of the tyrosine kinase substrate phospholipase C-gamma 1 in primary human breast carcinomas". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 88 (23): 10435–9. doi:10.1073/pnas.88.23.10435. ISSN 0027-8424. PMC 52943. PMID 1683701. 
  35. ↑ Banin, S; Truong O, Katz D R, Waterfield M D, Brickell P M, Gout I (August 1996). "Wiskott-Aldrich syndrome protein (WASp) is a binding partner for c-Src family protein-tyrosine kinases". Curr. Biol. (ENGLAND) 6 (8): 981–8. doi:10.1016/S0960-9822(02)00642-5. ISSN 0960-9822. PMID 8805332. 
  36. ↑ Finan, P M; Soames C J, Wilson L, Nelson D L, Stewart D M, Truong O, Hsuan J J, Kellie S (October 1996). "Identification of regions of the Wiskott-Aldrich syndrome protein responsible for association with selected Src homology 3 domains". J. Biol. Chem. (UNITED STATES) 271 (42): 26291–5. doi:10.1074/jbc.271.42.26291. ISSN 0021-9258. PMID 8824280. 
  37. ↑ 37.0 37.1 Tvorogov, Denis; Carpenter Graham (July 2002). "EGF-dependent association of phospholipase C-gamma1 with c-Cbl". Exp. Cell Res. (United States) 277 (1): 86–94. doi:10.1006/excr.2002.5545. ISSN 0014-4827. PMID 12061819. 
  38. ↑ Bedrin, M S; Abolafia C M, Thompson J F (July 1997). "Cytoskeletal association of epidermal growth factor receptor and associated signaling proteins is regulated by cell density in IEC-6 intestinal cells". J. Cell. Physiol. (UNITED STATES) 172 (1): 126–36. doi:10.1002/(SICI)1097-4652(199707)172:1<126::AID-JCP14>3.0.CO;2-A. ISSN 0021-9541. PMID 9207933. 
  39. ↑ Eriksson, A; Nånberg E, Rönnstrand L, Engström U, Hellman U, Rupp E, Carpenter G, Heldin C H, Claesson-Welsh L (March 1995). "Demonstration of functionally different interactions between phospholipase C-gamma and the two types of platelet-derived growth factor receptors". J. Biol. Chem. (UNITED STATES) 270 (13): 7773–81. doi:10.1074/jbc.270.13.7773. ISSN 0021-9258. PMID 7535778. 
  40. ↑ Chang, Jong-Soo; Seok Heon, Kwon Taeg-Kyu, Min Do Sik, Ahn Bong-Hyun, Lee Young Han, Suh Ju-Won, Kim Jong-Woo, Iwashita Shintaro, Omori Akira, Ichinose Sachiyo, Numata Osamu, Seo Jeong-Kon, Oh Yong-Seok, Suh Pann-Ghill (May 2002). "Interaction of elongation factor-1alpha and pleckstrin homology domain of phospholipase C-gamma 1 with activating its activity". J. Biol. Chem. (United States) 277 (22): 19697–702. doi:10.1074/jbc.M111206200. ISSN 0021-9258. PMID 11886851. 
  41. ↑ Zhang, W; Trible R P, Samelson L E (August 1998). "LAT palmitoylation: its essential role in membrane microdomain targeting and tyrosine phosphorylation during T cell activation". Immunity (UNITED STATES) 9 (2): 239–46. doi:10.1016/S1074-7613(00)80606-8. ISSN 1074-7613. PMID 9729044. 
  42. ↑ Paz, P E; Wang S, Clarke H, Lu X, Stokoe D, Abo A (June 2001). "Mapping the Zap-70 phosphorylation sites on LAT (linker for activation of T cells) required for recruitment and activation of signalling proteins in T cells". Biochem. J. (England) 356 (Pt 2): 461–71. doi:10.1042/0264-6021:3560461. ISSN 0264-6021. PMC 1221857. PMID 11368773. 
  43. ↑ Zhang, W; Sloan-Lancaster J, Kitchen J, Trible R P, Samelson L E (January 1998). "LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation". Cell (UNITED STATES) 92 (1): 83–92. doi:10.1016/S0092-8674(00)80901-0. ISSN 0092-8674. PMID 9489702. 
  44. ↑ Suzuki, Shingo; Mizutani Masaharu, Suzuki Kenji, Yamada Masashi, Kojima Masami, Hatanaka Hiroshi, Koizumi Shinichi (June 2002). "Brain-derived neurotrophic factor promotes interaction of the Nck2 adaptor protein with the TrkB tyrosine kinase receptor". Biochem. Biophys. Res. Commun. (United States) 294 (5): 1087–92. doi:10.1016/S0006-291X(02)00606-X. ISSN 0006-291X. PMID 12074588. 
  45. ↑ Graham, L J; Stoica B A, Shapiro M, DeBell K E, Rellahan B, Laborda J, Bonvini E (August 1998). "Sequences surrounding the Src-homology 3 domain of phospholipase Cgamma-1 increase the domain's association with Cbl". Biochem. Biophys. Res. Commun. (UNITED STATES) 249 (2): 537–41. doi:10.1006/bbrc.1998.9177. ISSN 0006-291X. PMID 9712732. 
  46. ↑ Kim, M J; Chang J S, Park S K, Hwang J I, Ryu S H, Suh P G (July 2000). "Direct interaction of SOS1 Ras exchange protein with the SH3 domain of phospholipase C-gamma1". Biochemistry (UNITED STATES) 39 (29): 8674–82. doi:10.1021/bi992558t. ISSN 0006-2960. PMID 10913276. 
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