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词条 PLCG1
释义

  1. Function

  2. Clinical significance

  3. Interactions

  4. See also

  5. References

{{Infobox_gene}}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]

Common to all PLC isozymes, PLCG1 consists of an N-terminal PH domain, which translocates PLC to the plasma membrane and binds PIP3;[5] four EF hands; an X and Y catalytic region comprising the TIM barrel; and a C-terminal C2 domain.[6] Specific to the PLCG isozymes is a large separation between the X and Y domains consisting of a split PH domain, tandem SH2 domains, and an SH3 domain.[6] The SH2 domains bind phosphorylated tyrosine residues on target proteins via their FLVR sequence motifs, activating the catalytic function of PLCg; and the SH3 domain binds to proline-rich sequences on the target protein.[6]

PLCG1 can be activated by receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases. For example, when activated, fibroblast growth factor receptor 1 and epidermal growth factor receptor are RTKs that have phosphorylated tyrosines, which provide docking sites for PLCG1 SH2 domains.[6] The activated RTKs phosphoylate PLCG1 at tyrosines located at position 472, 771, 775, 783, and 1254.[7] Non-receptor tyrosine kinases interact with PLCG1 in large complexes at the plasma membrane. For example, in T cells, Lck and Fyn (Src family kinases) phosphorylate immunoreceptor tyrosine-based activation motifs (ITAMs) on the T-cell antigen receptor (TCR).[6] The phosphorylated ITAMs recruit ZAP-70, which phosphorylates tyrosines in LAT and SLP-76. PLCg1 binds to LAT through its n-terminal SH2 domain and to SLP-76 via its SH3 domain.[6]

Has been shown to interact with CISH which negatively regulates it by targeting it for degradation.[8] The deletion of Cish in effector T cells has been shown to augment TCR signaling and subsequent effector cytokine release, proliferation and survival. The adoptive transfer of tumor-specific effector T cells knocked out or knocked down for CISH resulted in a significant increase in functional avidity and long-term tumor immunity. There are no changes in activity or phosphorylation of Cish's purported target, STAT5 in either the presence or absence of Cish.

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.[9][10]

Interactions

PLCG1 has been shown to interact with:

{{div col|colwidth=20em}}
  • BAG3,[11]
  • CD117,[12][13]
  • CD31,[14]
  • Cbl gene[20][15]
  • CISH[8]
  • Epidermal growth factor receptor,[16][17]
  • Eukaryotic translation elongation factor 1 alpha 1,[18]
  • FLT1,[19]
  • GAB1,[20][21]
  • GIT1,[22]
  • Grb2,[23][24][25]
  • HER2/neu,[26][27]
  • IRS2,[28]
  • ITK,[29][30]
  • KHDRBS1,[31][32][33]
  • Linker of activated T cells,[34][35][36]
  • Lymphocyte cytosolic protein 2,[37]
  • PDGFRA,[38]
  • PLD2,[39]
  • RHOA,[40]
  • SOS1,[25][41]
  • TUB,[42]
  • TrkA,[43][44][45][46]
  • TrkB,[45][47]
  • VAV1,[48] and
  • Wiskott-Aldrich syndrome protein.[49][50]
{{Div col end}}

See also

  • Phospholipase C
{{Clear}}

References

1. ^{{cite journal | vauthors = Bristol A, Hall SM, Kriz RW, Stahl ML, Fan YS, Byers MG, Eddy RL, Shows TB, Knopf JL | title = Phospholipase C-148: chromosomal location and deletion mapping of functional domains | journal = Cold Spring Harbor Symposia on Quantitative Biology | volume = 53 Pt 2 | issue = 2 | pages = 915–20 | year = 1988 | pmid = 3254788 | doi = 10.1101/sqb.1988.053.01.105 }}
2. ^{{cite journal | vauthors = Burgess WH, Dionne CA, Kaplow J, Mudd R, Friesel R, Zilberstein A, Schlessinger J, Jaye M | title = Characterization and cDNA cloning of phospholipase C-gamma, a major substrate for heparin-binding growth factor 1 (acidic fibroblast growth factor)-activated tyrosine kinase | journal = Molecular and Cellular Biology | volume = 10 | issue = 9 | pages = 4770–7 | date = September 1990 | pmid = 2167438 | pmc = 361079 | doi = 10.1128/mcb.10.9.4770}}
3. ^{{cite journal | vauthors = Phillips-Mason PJ, Kaur H, Burden-Gulley SM, Craig SE, Brady-Kalnay SM | title = Identification of phospholipase C gamma1 as a protein tyrosine phosphatase mu substrate that regulates cell migration | journal = Journal of Cellular Biochemistry | volume = 112 | issue = 1 | pages = 39–48 | date = January 2011 | pmid = 20506511 | pmc = 3031780 | doi = 10.1002/jcb.22710 }}
4. ^{{Cite web| title = Entrez Gene: PLCG1 phospholipase C, gamma 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5335| accessdate = }}
5. ^{{cite journal | vauthors = Singh SM, Murray D | title = Molecular modeling of the membrane targeting of phospholipase C pleckstrin homology domains | journal = Protein Science | volume = 12 | issue = 9 | pages = 1934–53 | date = September 2003 | pmid = 12930993 | pmc = 2323991 | doi = 10.1110/ps.0358803 }}
6. ^{{cite book | vauthors = Gresset A, Sondek J, Harden TK | title = The phospholipase C isozymes and their regulation | journal = Sub-Cellular Biochemistry | volume = 58 | pages = 61–94 | date = March 2012 | pmid = 22403074 | pmc = 3638883 | doi = 10.1007/978-94-007-3012-0_3 | series = Subcellular Biochemistry | isbn = 978-94-007-3011-3 }}
7. ^{{cite journal | vauthors = Bae JH, Lew ED, Yuzawa S, Tomé F, Lax I, Schlessinger J | title = The selectivity of receptor tyrosine kinase signaling is controlled by a secondary SH2 domain binding site | journal = Cell | volume = 138 | issue = 3 | pages = 514–24 | date = August 2009 | pmid = 19665973 | pmc = 4764080 | doi = 10.1016/j.cell.2009.05.028 }}
8. ^{{cite journal | vauthors = Palmer DC, Guittard GC, Franco Z, Crompton JG, Eil RL, Patel SJ, Ji Y, Van Panhuys N, Klebanoff CA, Sukumar M, Clever D, Chichura A, Roychoudhuri R, Varma R, Wang E, Gattinoni L, Marincola FM, Balagopalan L, Samelson LE, Restifo NP | title = Cish actively silences TCR signaling in CD8+ T cells to maintain tumor tolerance | journal = The Journal of Experimental Medicine | volume = 212 | issue = 12 | pages = 2095–113 | date = November 2015 | pmid = 26527801 | pmc = 4647263 | doi = 10.1084/jem.20150304 }}
9. ^{{Cite web| url = https://www.telegraph.co.uk/health/healthnews/3758314/Scientists-may-be-able-to-stop-cancer-spreading-round-the-body.html | title = Scientists may be able to stop cancer spreading round the body | author = Smith R | authorlink = | date = 2008-12-14 | work = Health News | publisher = Telegraph.co.uk | pages = | archiveurl = | archivedate = | quote = | accessdate = 2008-12-17}}
10. ^{{cite journal | vauthors = 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 | title = Phospholipase Cgamma1 is required for metastasis development and progression | journal = Cancer Research | volume = 68 | issue = 24 | pages = 10187–96 | date = December 2008 | pmid = 19074886 | doi = 10.1158/0008-5472.CAN-08-1181 }}
11. ^{{cite journal | vauthors = Doong H, Price J, Kim YS, Gasbarre C, Probst J, Liotta LA, Blanchette J, Rizzo K, Kohn E | title = CAIR-1/BAG-3 forms an EGF-regulated ternary complex with phospholipase C-gamma and Hsp70/Hsc70 | journal = Oncogene | volume = 19 | issue = 38 | pages = 4385–95 | date = September 2000 | pmid = 10980614 | doi = 10.1038/sj.onc.1203797 }}
12. ^{{cite journal | vauthors = van Dijk TB, van Den Akker E, Amelsvoort MP, Mano H, Löwenberg B, von Lindern M | title = Stem cell factor induces phosphatidylinositol 3'-kinase-dependent Lyn/Tec/Dok-1 complex formation in hematopoietic cells | journal = Blood | volume = 96 | issue = 10 | pages = 3406–13 | date = November 2000 | pmid = 11071635 | doi = }}
13. ^{{cite journal | vauthors = Jhun BH, Rivnay B, Price D, Avraham H | title = The MATK tyrosine kinase interacts in a specific and SH2-dependent manner with c-Kit | journal = The Journal of Biological Chemistry | volume = 270 | issue = 16 | pages = 9661–6 | date = April 1995 | pmid = 7536744 | doi = 10.1074/jbc.270.16.9661 }}
14. ^{{cite journal | vauthors = Pumphrey NJ, Taylor V, Freeman S, Douglas MR, Bradfield PF, Young SP, Lord JM, Wakelam MJ, Bird IN, Salmon M, Buckley CD | title = Differential association of cytoplasmic signalling molecules SHP-1, SHP-2, SHIP and phospholipase C-gamma1 with PECAM-1/CD31 | journal = FEBS Letters | volume = 450 | issue = 1–2 | pages = 77–83 | date = April 1999 | pmid = 10350061 | doi = 10.1016/s0014-5793(99)00446-9 }}
15. ^{{cite journal | vauthors = Graham LJ, Stoica BA, Shapiro M, DeBell KE, Rellahan B, Laborda J, Bonvini E | title = Sequences surrounding the Src-homology 3 domain of phospholipase Cgamma-1 increase the domain's association with Cbl | journal = Biochemical and Biophysical Research Communications | volume = 249 | issue = 2 | pages = 537–41 | date = August 1998 | pmid = 9712732 | doi = 10.1006/bbrc.1998.9177 }}
16. ^{{cite journal | vauthors = Tvorogov D, Carpenter G | title = EGF-dependent association of phospholipase C-gamma1 with c-Cbl | journal = Experimental Cell Research | volume = 277 | issue = 1 | pages = 86–94 | date = July 2002 | pmid = 12061819 | doi = 10.1006/excr.2002.5545 }}
17. ^{{cite journal | vauthors = Bedrin MS, Abolafia CM, Thompson JF | title = Cytoskeletal association of epidermal growth factor receptor and associated signaling proteins is regulated by cell density in IEC-6 intestinal cells | journal = Journal of Cellular Physiology | volume = 172 | issue = 1 | pages = 126–36 | date = July 1997 | pmid = 9207933 | doi = 10.1002/(SICI)1097-4652(199707)172:1<126::AID-JCP14>3.0.CO;2-A }}
18. ^{{cite journal | vauthors = Chang JS, Seok H, Kwon TK, Min DS, Ahn BH, Lee YH, Suh JW, Kim JW, Iwashita S, Omori A, Ichinose S, Numata O, Seo JK, Oh YS, Suh PG | title = Interaction of elongation factor-1alpha and pleckstrin homology domain of phospholipase C-gamma 1 with activating its activity | journal = The Journal of Biological Chemistry | volume = 277 | issue = 22 | pages = 19697–702 | date = May 2002 | pmid = 11886851 | doi = 10.1074/jbc.M111206200 }}
19. ^{{cite journal | vauthors = Cunningham SA, Arrate MP, Brock TA, Waxham MN | title = Interactions of FLT-1 and KDR with phospholipase C gamma: identification of the phosphotyrosine binding sites | journal = Biochemical and Biophysical Research Communications | volume = 240 | issue = 3 | pages = 635–9 | date = November 1997 | pmid = 9398617 | doi = 10.1006/bbrc.1997.7719 }}
20. ^{{cite journal | vauthors = Ueno E, Haruta T, Uno T, Usui I, Iwata M, Takano A, Kawahara J, Sasaoka T, Ishibashi O, Kobayashi M | title = Potential role of Gab1 and phospholipase C-gamma in osmotic shock-induced glucose uptake in 3T3-L1 adipocytes | journal = Hormone and Metabolic Research = Hormon- und Stoffwechselforschung = Hormones et Metabolisme | volume = 33 | issue = 7 | pages = 402–6 | date = July 2001 | pmid = 11507676 | doi = 10.1055/s-2001-16227 }}
21. ^{{cite journal | vauthors = Holgado-Madruga M, Emlet DR, Moscatello DK, Godwin AK, Wong AJ | title = A Grb2-associated docking protein in EGF- and insulin-receptor signalling | journal = Nature | volume = 379 | issue = 6565 | pages = 560–4 | date = February 1996 | pmid = 8596638 | doi = 10.1038/379560a0 }}
22. ^{{cite journal | vauthors = Haendeler J, Yin G, Hojo Y, Saito Y, Melaragno M, Yan C, Sharma VK, Heller M, Aebersold R, Berk BC | title = GIT1 mediates Src-dependent activation of phospholipase Cgamma by angiotensin II and epidermal growth factor | journal = The Journal of Biological Chemistry | volume = 278 | issue = 50 | pages = 49936–44 | date = December 2003 | pmid = 14523024 | doi = 10.1074/jbc.M307317200 }}
23. ^{{cite journal | vauthors = Pei Z, Maloney JA, Yang L, Williamson JR | title = A new function for phospholipase C-gamma1: coupling to the adaptor protein GRB2 | journal = Archives of Biochemistry and Biophysics | volume = 345 | issue = 1 | pages = 103–10 | date = September 1997 | pmid = 9281317 | doi = 10.1006/abbi.1997.0245 }}
24. ^{{cite journal | vauthors = Nel AE, Gupta S, Lee L, Ledbetter JA, Kanner SB | title = 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 | journal = The Journal of Biological Chemistry | volume = 270 | issue = 31 | pages = 18428–36 | date = August 1995 | pmid = 7629168 | doi = 10.1074/jbc.270.31.18428 }}
25. ^{{cite journal | vauthors = Scholler JK, Perez-Villar JJ, O'Day K, Kanner SB | title = Engagement of the T lymphocyte antigen receptor regulates association of son-of-sevenless homologues with the SH3 domain of phospholipase Cgamma1 | journal = European Journal of Immunology | volume = 30 | issue = 8 | pages = 2378–87 | date = August 2000 | pmid = 10940929 | doi = 10.1002/1521-4141(2000)30:8<2378::AID-IMMU2378>3.0.CO;2-E }}
26. ^{{cite journal | vauthors = Peles E, Levy RB, Or E, Ullrich A, Yarden Y | title = Oncogenic forms of the neu/HER2 tyrosine kinase are permanently coupled to phospholipase C gamma | journal = The EMBO Journal | volume = 10 | issue = 8 | pages = 2077–86 | date = August 1991 | pmid = 1676673 | pmc = 452891 | doi = 10.1002/j.1460-2075.1991.tb07739.x}}
27. ^{{cite journal | vauthors = Arteaga CL, Johnson MD, Todderud G, Coffey RJ, Carpenter G, Page DL | title = Elevated content of the tyrosine kinase substrate phospholipase C-gamma 1 in primary human breast carcinomas | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 88 | issue = 23 | pages = 10435–9 | date = December 1991 | pmid = 1683701 | pmc = 52943 | doi = 10.1073/pnas.88.23.10435 }}
28. ^{{cite journal | vauthors = Sozzani P, Hasan L, Séguélas MH, Caput D, Ferrara P, Pipy B, Cambon C | title = 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 | journal = Biochemical and Biophysical Research Communications | volume = 244 | issue = 3 | pages = 665–70 | date = March 1998 | pmid = 9535722 | doi = 10.1006/bbrc.1998.8314 }}
29. ^{{cite journal | vauthors = Perez-Villar JJ, Kanner SB | title = Regulated association between the tyrosine kinase Emt/Itk/Tsk and phospholipase-C gamma 1 in human T lymphocytes | journal = Journal of Immunology | volume = 163 | issue = 12 | pages = 6435–41 | date = December 1999 | pmid = 10586033 | doi = }}
30. ^{{cite journal | vauthors = Hao S, August A | title = The proline rich region of the Tec homology domain of ITK regulates its activity | journal = FEBS Letters | volume = 525 | issue = 1–3 | pages = 53–8 | date = August 2002 | pmid = 12163161 | doi = 10.1016/s0014-5793(02)03066-1 }}
31. ^{{cite journal | vauthors = Oneyama C, Nakano H, Sharma SV | title = UCS15A, a novel small molecule, SH3 domain-mediated protein-protein interaction blocking drug | journal = Oncogene | volume = 21 | issue = 13 | pages = 2037–50 | date = March 2002 | pmid = 11960376 | doi = 10.1038/sj.onc.1205271 }}
32. ^{{cite journal | vauthors = Jabado N, Jauliac S, Pallier A, Bernard F, Fischer A, Hivroz C | title = Sam68 association with p120GAP in CD4+ T cells is dependent on CD4 molecule expression | journal = Journal of Immunology | volume = 161 | issue = 6 | pages = 2798–803 | date = September 1998 | pmid = 9743338 | doi = }}
33. ^{{cite journal | vauthors = Shen Z, Batzer A, Koehler JA, Polakis P, Schlessinger J, Lydon NB, Moran MF | title = Evidence for SH3 domain directed binding and phosphorylation of Sam68 by Src | journal = Oncogene | volume = 18 | issue = 33 | pages = 4647–53 | date = August 1999 | pmid = 10467411 | doi = 10.1038/sj.onc.1203079 }}
34. ^{{cite journal | vauthors = Zhang W, Trible RP, Samelson LE | title = LAT palmitoylation: its essential role in membrane microdomain targeting and tyrosine phosphorylation during T cell activation | journal = Immunity | volume = 9 | issue = 2 | pages = 239–46 | date = August 1998 | pmid = 9729044 | doi = 10.1016/s1074-7613(00)80606-8 }}
35. ^{{cite journal | vauthors = Paz PE, Wang S, Clarke H, Lu X, Stokoe D, Abo A | title = 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 | journal = The Biochemical Journal | volume = 356 | issue = Pt 2 | pages = 461–71 | date = June 2001 | pmid = 11368773 | pmc = 1221857 | doi = 10.1042/0264-6021:3560461 }}
36. ^{{cite journal | vauthors = Zhang W, Sloan-Lancaster J, Kitchen J, Trible RP, Samelson LE | title = LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation | journal = Cell | volume = 92 | issue = 1 | pages = 83–92 | date = January 1998 | pmid = 9489702 | doi = 10.1016/S0092-8674(00)80901-0 }}
37. ^{{cite journal | vauthors = Yablonski D, Kadlecek T, Weiss A | title = 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 | journal = Molecular and Cellular Biology | volume = 21 | issue = 13 | pages = 4208–18 | date = July 2001 | pmid = 11390650 | pmc = 87082 | doi = 10.1128/MCB.21.13.4208-4218.2001 }}
38. ^{{cite journal | vauthors = Eriksson A, Nånberg E, Rönnstrand L, Engström U, Hellman U, Rupp E, Carpenter G, Heldin CH, Claesson-Welsh L | title = Demonstration of functionally different interactions between phospholipase C-gamma and the two types of platelet-derived growth factor receptors | journal = The Journal of Biological Chemistry | volume = 270 | issue = 13 | pages = 7773–81 | date = March 1995 | pmid = 7535778 | doi = 10.1074/jbc.270.13.7773 }}
39. ^{{cite journal | vauthors = Jang IH, Lee S, Park JB, Kim JH, Lee CS, Hur EM, Kim IS, Kim KT, Yagisawa H, Suh PG, Ryu SH | title = The direct interaction of phospholipase C-gamma 1 with phospholipase D2 is important for epidermal growth factor signaling | journal = The Journal of Biological Chemistry | volume = 278 | issue = 20 | pages = 18184–90 | date = May 2003 | pmid = 12646582 | doi = 10.1074/jbc.M208438200 }}
40. ^{{cite journal | vauthors = Thodeti CK, Massoumi R, Bindslev L, Sjölander A | title = Leukotriene D4 induces association of active RhoA with phospholipase C-gamma1 in intestinal epithelial cells | journal = The Biochemical Journal | volume = 365 | issue = Pt 1 | pages = 157–63 | date = July 2002 | pmid = 12071848 | pmc = 1222665 | doi = 10.1042/BJ20020248 }}
41. ^{{cite journal | vauthors = Kim MJ, Chang JS, Park SK, Hwang JI, Ryu SH, Suh PG | title = Direct interaction of SOS1 Ras exchange protein with the SH3 domain of phospholipase C-gamma1 | journal = Biochemistry | volume = 39 | issue = 29 | pages = 8674–82 | date = July 2000 | pmid = 10913276 | doi = 10.1021/bi992558t }}
42. ^{{cite journal | vauthors = Kapeller R, Moriarty A, Strauss A, Stubdal H, Theriault K, Siebert E, Chickering T, Morgenstern JP, Tartaglia LA, Lillie J | title = Tyrosine phosphorylation of tub and its association with Src homology 2 domain-containing proteins implicate tub in intracellular signaling by insulin | journal = The Journal of Biological Chemistry | volume = 274 | issue = 35 | pages = 24980–6 | date = August 1999 | pmid = 10455176 | doi = 10.1074/jbc.274.35.24980 }}
43. ^{{cite journal | vauthors = Ohmichi M, Decker SJ, Pang L, Saltiel AR | title = 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 | journal = Biochemical and Biophysical Research Communications | volume = 179 | issue = 1 | pages = 217–23 | date = August 1991 | pmid = 1715690 | doi = 10.1016/0006-291x(91)91357-i }}
44. ^{{cite journal | vauthors = Qian X, Riccio A, Zhang Y, Ginty DD | title = Identification and characterization of novel substrates of Trk receptors in developing neurons | journal = Neuron | volume = 21 | issue = 5 | pages = 1017–29 | date = November 1998 | pmid = 9856458 | doi = 10.1016/s0896-6273(00)80620-0 }}
45. ^{{cite journal | vauthors = Meakin SO, MacDonald JI, Gryz EA, Kubu CJ, Verdi JM | title = The signaling adapter FRS-2 competes with Shc for binding to the nerve growth factor receptor TrkA. A model for discriminating proliferation and differentiation | journal = The Journal of Biological Chemistry | volume = 274 | issue = 14 | pages = 9861–70 | date = April 1999 | pmid = 10092678 | doi = 10.1074/jbc.274.14.9861 }}
46. ^{{cite journal | vauthors = Koch A, Mancini A, Stefan M, Niedenthal R, Niemann H, Tamura T | title = Direct interaction of nerve growth factor receptor, TrkA, with non-receptor tyrosine kinase, c-Abl, through the activation loop | journal = FEBS Letters | volume = 469 | issue = 1 | pages = 72–6 | date = March 2000 | pmid = 10708759 | doi = 10.1016/s0014-5793(00)01242-4 }}
47. ^{{cite journal | vauthors = Suzuki S, Mizutani M, Suzuki K, Yamada M, Kojima M, Hatanaka H, Koizumi S | title = Brain-derived neurotrophic factor promotes interaction of the Nck2 adaptor protein with the TrkB tyrosine kinase receptor | journal = Biochemical and Biophysical Research Communications | volume = 294 | issue = 5 | pages = 1087–92 | date = June 2002 | pmid = 12074588 | doi = 10.1016/S0006-291X(02)00606-X }}
48. ^{{cite journal | vauthors = Bertagnolo V, Marchisio M, Volinia S, Caramelli E, Capitani S | title = Nuclear association of tyrosine-phosphorylated Vav to phospholipase C-gamma1 and phosphoinositide 3-kinase during granulocytic differentiation of HL-60 cells | journal = FEBS Letters | volume = 441 | issue = 3 | pages = 480–4 | date = December 1998 | pmid = 9891995 | doi = 10.1016/s0014-5793(98)01593-2 }}
49. ^{{cite journal | vauthors = Banin S, Truong O, Katz DR, Waterfield MD, Brickell PM, Gout I | title = Wiskott-Aldrich syndrome protein (WASp) is a binding partner for c-Src family protein-tyrosine kinases | journal = Current Biology | volume = 6 | issue = 8 | pages = 981–8 | date = August 1996 | pmid = 8805332 | doi = 10.1016/s0960-9822(02)00642-5 }}
50. ^{{cite journal | vauthors = Finan PM, Soames CJ, Wilson L, Nelson DL, Stewart DM, Truong O, Hsuan JJ, Kellie S | title = Identification of regions of the Wiskott-Aldrich syndrome protein responsible for association with selected Src homology 3 domains | journal = The Journal of Biological Chemistry | volume = 271 | issue = 42 | pages = 26291–5 | date = October 1996 | pmid = 8824280 | doi = 10.1074/jbc.271.42.26291 }}
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2 : Peripheral membrane proteins|EC 3.1.4

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