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Lymphocyte cytosolic protein 2 (SH2 domain containing leukocyte protein of 76kDa)
Identifiers
Symbols LCP2; SLP-76; SLP76
External IDs OMIM: 601603 MGI: 1321402 HomoloGene: 4065
RNA expression pattern
PBB GE LCP2 205269 at tn.png
PBB GE LCP2 205270 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 3937 16822
Ensembl ENSG00000043462 ENSMUSG00000002699
UniProt Q13094 Q3U5Y3
RefSeq NM_005565 (mRNA) NM_010696 (mRNA)
NP_005556 (protein) NP_034826 (protein)
Location Chr 5:
169.61 - 169.66 Mb		 Chr 11:
33.95 - 33.99 Mb
PubMed search [1] [2]

Lymphocyte cytosolic protein 2 (SH2 domain containing leukocyte protein of 76kDa), also known as LCP2 or SLP-76, is a gene which encodes a signal transducing adaptor protein.[1]

SLP-76 was originally identified as a substrate of the ZAP-70 protein tyrosine kinase following T cell receptor (TCR) ligation in the leukemic T cell line Jurkat. The SLP-76 locus has been localized to human chromosome 5q33 and the gene structure has been partially characterized in mice. The human and murine cDNAs both encode 533 amino acid proteins that are 72% identical and comprised of three modular domains. The NH2-terminus contains an acidic region that includes a PEST domain and several tyrosine residues which are phosphorylated following TCR ligation. SLP-76 also contains a central proline-rich domain and a COOH-terminal SH2 domain. A number of additional proteins have been identified that associate with SLP-76 both constitutively and inducibly following receptor ligation, supporting the notion that SLP-76 functions as an adaptor or scaffold protein. Studies using SLP-76 deficient T cell lines or mice have provided strong evidence that SLP-76 plays a positive role in promoting T cell development and activation as well as mast cell and platelet function.[1]

Contents

[edit] Interactions

Lymphocyte cytosolic protein 2 has been shown to interact with SHB,[2] PLCG1,[3] PTPN6,[4][5] LYN,[6] NCK1,[7][8] Cbl gene,[9][10] GRAP2,[11][12][13][14] PIK3R1,[7] Grb2,[15][16][10][17][14] ITK[7][18] and VAV1.[19][20]

[edit] References

  1. ^ a b "Entrez Gene: LCP2 lymphocyte cytosolic protein 2 (SH2 domain containing leukocyte protein of 76kDa)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3937. 
  2. ^ Lindholm, Cecilia K; Henriksson Maria L, Hallberg Bengt, Welsh Michael (Jul. 2002). "Shb links SLP-76 and Vav with the CD3 complex in Jurkat T cells". Eur. J. Biochem. (Germany) 269 (13): 3279-88. ISSN 0014-2956. PMID 12084069. 
  3. ^ Yablonski, D; Kadlecek T, Weiss A (Jul. 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. PMID 11390650. 
  4. ^ Binstadt, B A; Billadeau D D, Jevremović D, Williams B L, Fang N, Yi T, Koretzky G A, Abraham R T, Leibson P J (Oct. 1998). "SLP-76 is a direct substrate of SHP-1 recruited to killer cell inhibitory receptors". J. Biol. Chem. (UNITED STATES) 273 (42): 27518-23. ISSN 0021-9258. PMID 9765283. 
  5. ^ Mizuno, K; Katagiri T, Hasegawa K, Ogimoto M, Yakura H (Aug. 1996). "Hematopoietic cell phosphatase, SHP-1, is constitutively associated with the SH2 domain-containing leukocyte protein, SLP-76, in B cells". J. Exp. Med. (UNITED STATES) 184 (2): 457-63. ISSN 0022-1007. PMID 8760799. 
  6. ^ Gross, B S; Lee J R, Clements J L, Turner M, Tybulewicz V L, Findell P R, Koretzky G A, Watson S P (Feb. 1999). "Tyrosine phosphorylation of SLP-76 is downstream of Syk following stimulation of the collagen receptor in platelets". J. Biol. Chem. (UNITED STATES) 274 (9): 5963-71. ISSN 0021-9258. PMID 10026222. 
  7. ^ a b c Shim, Eun Kyung; Moon Chang Suk, Lee Gi Yeon, Ha Yun Jung, Chae Suhn-Kee, Lee Jong Ran (Sep. 2004). "Association of the Src homology 2 domain-containing leukocyte phosphoprotein of 76 kD (SLP-76) with the p85 subunit of phosphoinositide 3-kinase". FEBS Lett. (Netherlands) 575 (1-3): 35-40. doi:10.1016/j.febslet.2004.07.090. ISSN 0014-5793. PMID 15388330. 
  8. ^ Wunderlich, L; Faragó A, Downward J, Buday L (Apr. 1999). "Association of Nck with tyrosine-phosphorylated SLP-76 in activated T lymphocytes". Eur. J. Immunol. (GERMANY) 29 (4): 1068-75. ISSN 0014-2980. PMID 10229072. 
  9. ^ Park, R K; Izadi K D, Deo Y M, Durden D L (Sep. 1999). "Role of Src in the modulation of multiple adaptor proteins in FcalphaRI oxidant signaling". Blood (UNITED STATES) 94 (6): 2112-20. ISSN 0006-4971. PMID 10477741. 
  10. ^ a b Erdreich-Epstein, A; Liu M, Kant A M, Izadi K D, Nolta J A, Durden D L (Apr. 1999). "Cbl functions downstream of Src kinases in Fc gamma RI signaling in primary human macrophages". J. Leukoc. Biol. (UNITED STATES) 65 (4): 523-34. ISSN 0741-5400. PMID 10204582. 
  11. ^ Rual, Jean-François; Venkatesan Kavitha, Hao Tong, Hirozane-Kishikawa Tomoko, Dricot Amélie, Li Ning, Berriz Gabriel F, Gibbons Francis D, Dreze Matija, Ayivi-Guedehoussou Nono, Klitgord Niels, Simon Christophe, Boxem Mike, Milstein Stuart, Rosenberg Jennifer, Goldberg Debra S, Zhang Lan V, Wong Sharyl L, Franklin Giovanni, Li Siming, Albala Joanna S, Lim Janghoo, Fraughton Carlene, Llamosas Estelle, Cevik Sebiha, Bex Camille, Lamesch Philippe, Sikorski Robert S, Vandenhaute Jean, Zoghbi Huda Y, Smolyar Alex, Bosak Stephanie, Sequerra Reynaldo, Doucette-Stamm Lynn, Cusick Michael E, Hill David E, Roth Frederick P, Vidal Marc (Oct. 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature (England) 437 (7062): 1173-8. doi:10.1038/nature04209. PMID 16189514. 
  12. ^ Ellis, J H; Ashman C, Burden M N, Kilpatrick K E, Morse M A, Hamblin P A (Jun. 2000). "GRID: a novel Grb-2-related adapter protein that interacts with the activated T cell costimulatory receptor CD28". J. Immunol. (UNITED STATES) 164 (11): 5805-14. ISSN 0022-1767. PMID 10820259. 
  13. ^ Liu, S K; Fang N, Koretzky G A, McGlade C J (Jan. 1999). "The hematopoietic-specific adaptor protein gads functions in T-cell signaling via interactions with the SLP-76 and LAT adaptors". Curr. Biol. (ENGLAND) 9 (2): 67-75. ISSN 0960-9822. PMID 10021361. 
  14. ^ a b Asada, H; Ishii N, Sasaki Y, Endo K, Kasai H, Tanaka N, Takeshita T, Tsuchiya S, Konno T, Sugamura K (May. 1999). "Grf40, A novel Grb2 family member, is involved in T cell signaling through interaction with SLP-76 and LAT". J. Exp. Med. (UNITED STATES) 189 (9): 1383-90. ISSN 0022-1007. PMID 10224278. 
  15. ^ Lewitzky, M; Kardinal C, Gehring N H, Schmidt E K, Konkol B, Eulitz M, Birchmeier W, Schaeper U, Feller S M (Mar. 2001). "The C-terminal SH3 domain of the adapter protein Grb2 binds with high affinity to sequences in Gab1 and SLP-76 which lack the SH3-typical P-x-x-P core motif". Oncogene (England) 20 (9): 1052-62. doi:10.1038/sj.onc.1204202. ISSN 0950-9232. PMID 11314042. 
  16. ^ Robinson, A; Gibbins J, Rodríguez-Liñares B, Finan P M, Wilson L, Kellie S, Findell P, Watson S P (Jul. 1996). "Characterization of Grb2-binding proteins in human platelets activated by Fc gamma RIIA cross-linking". Blood (UNITED STATES) 88 (2): 522-30. ISSN 0006-4971. PMID 8695800. 
  17. ^ Hendricks-Taylor, L R; Motto D G, Zhang J, Siraganian R P, Koretzky G A (Jan. 1997). "SLP-76 is a substrate of the high affinity IgE receptor-stimulated protein tyrosine kinases in rat basophilic leukemia cells". J. Biol. Chem. (UNITED STATES) 272 (2): 1363-7. ISSN 0021-9258. PMID 8995445. 
  18. ^ Bunnell, S C; Diehn M, Yaffe M B, Findell P R, Cantley L C, Berg L J (Jan. 2000). "Biochemical interactions integrating Itk with the T cell receptor-initiated signaling cascade". J. Biol. Chem. (UNITED STATES) 275 (3): 2219-30. ISSN 0021-9258. PMID 10636929. 
  19. ^ Raab, M; da Silva A J, Findell P R, Rudd C E (Feb. 1997). "Regulation of Vav-SLP-76 binding by ZAP-70 and its relevance to TCR zeta/CD3 induction of interleukin-2". Immunity (UNITED STATES) 6 (2): 155-64. ISSN 1074-7613. PMID 9047237. 
  20. ^ Onodera, H; Motto D G, Koretzky G A, Rothstein D M (Sep. 1996). "Differential regulation of activation-induced tyrosine phosphorylation and recruitment of SLP-76 to Vav by distinct isoforms of the CD45 protein-tyrosine phosphatase". J. Biol. Chem. (UNITED STATES) 271 (36): 22225-30. ISSN 0021-9258. PMID 8703037. 

[edit] Further reading

  • Jackman JK, Motto DG, Sun Q, et al. (1995). "Molecular cloning of SLP-76, a 76-kDa tyrosine phosphoprotein associated with Grb2 in T cells.". J. Biol. Chem. 270 (13): 7029–32. doi:10.1074/jbc.270.13.7029. PMID 7706237. 
  • Sunden SL, Carr LL, Clements JL, et al. (1996). "Polymorphism in and localization of the gene LCP2 (SLP-76) to chromosome 5q33.1-qter.". Genomics 35 (1): 269–70. doi:10.1006/geno.1996.0354. PMID 8661136. 
  • Motto DG, Ross SE, Wu J, et al. (1996). "Implication of the GRB2-associated phosphoprotein SLP-76 in T cell receptor-mediated interleukin 2 production.". J. Exp. Med. 183 (4): 1937–43. doi:10.1084/jem.183.4.1937. PMID 8666952. 
  • Wardenburg JB, Fu C, Jackman JK, et al. (1996). "Phosphorylation of SLP-76 by the ZAP-70 protein-tyrosine kinase is required for T-cell receptor function.". J. Biol. Chem. 271 (33): 19641–4. doi:10.1074/jbc.271.33.19641. PMID 8702662. 
  • Onodera H, Motto DG, Koretzky GA, Rothstein DM (1996). "Differential regulation of activation-induced tyrosine phosphorylation and recruitment of SLP-76 to Vav by distinct isoforms of the CD45 protein-tyrosine phosphatase.". J. Biol. Chem. 271 (36): 22225–30. doi:10.1074/jbc.271.36.22225. PMID 8703037. 
  • Mizuno K, Katagiri T, Hasegawa K, et al. (1996). "Hematopoietic cell phosphatase, SHP-1, is constitutively associated with the SH2 domain-containing leukocyte protein, SLP-76, in B cells.". J. Exp. Med. 184 (2): 457–63. doi:10.1084/jem.184.2.457. PMID 8760799. 
  • Raab M, da Silva AJ, Findell PR, Rudd CE (1997). "Regulation of Vav-SLP-76 binding by ZAP-70 and its relevance to TCR zeta/CD3 induction of interleukin-2.". Immunity 6 (2): 155–64. doi:10.1016/S1074-7613(00)80422-7. PMID 9047237. 
  • Musci MA, Hendricks-Taylor LR, Motto DG, et al. (1997). "Molecular cloning of SLAP-130, an SLP-76-associated substrate of the T cell antigen receptor-stimulated protein tyrosine kinases.". J. Biol. Chem. 272 (18): 11674–7. doi:10.1074/jbc.272.18.11674. PMID 9115214. 
  • da Silva AJ, Li Z, de Vera C, et al. (1997). "Cloning of a novel T-cell protein FYB that binds FYN and SH2-domain-containing leukocyte protein 76 and modulates interleukin 2 production.". Proc. Natl. Acad. Sci. U.S.A. 94 (14): 7493–8. doi:10.1073/pnas.94.14.7493. PMID 9207119. 
  • Fu C, Chan AC (1997). "Identification of two tyrosine phosphoproteins, pp70 and pp68, which interact with phospholipase Cgamma, Grb2, and Vav after B cell antigen receptor activation.". J. Biol. Chem. 272 (43): 27362–8. doi:10.1074/jbc.272.43.27362. PMID 9341187. 
  • Zhang W, Sloan-Lancaster J, Kitchen J, et al. (1998). "LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation.". Cell 92 (1): 83–92. doi:10.1016/S0092-8674(00)80901-0. PMID 9489702. 
  • Fu C, Turck CW, Kurosaki T, Chan AC (1998). "BLNK: a central linker protein in B cell activation.". Immunity 9 (1): 93–103. doi:10.1016/S1074-7613(00)80591-9. PMID 9697839. 
  • Chu J, Liu Y, Koretzky GA, Durden DL (1998). "SLP-76-Cbl-Grb2-Shc interactions in FcgammaRI signaling.". Blood 92 (5): 1697–706. PMID 9716598. 
  • Binstadt BA, Billadeau DD, Jevremović D, et al. (1998). "SLP-76 is a direct substrate of SHP-1 recruited to killer cell inhibitory receptors.". J. Biol. Chem. 273 (42): 27518–23. doi:10.1074/jbc.273.42.27518. PMID 9765283. 
  • Liu SK, Fang N, Koretzky GA, McGlade CJ (1999). "The hematopoietic-specific adaptor protein gads functions in T-cell signaling via interactions with the SLP-76 and LAT adaptors.". Curr. Biol. 9 (2): 67–75. doi:10.1016/S0960-9822(99)80017-7. PMID 10021361. 
  • Gross BS, Lee JR, Clements JL, et al. (1999). "Tyrosine phosphorylation of SLP-76 is downstream of Syk following stimulation of the collagen receptor in platelets.". J. Biol. Chem. 274 (9): 5963–71. doi:10.1074/jbc.274.9.5963. PMID 10026222. 
  • Erdreich-Epstein A, Liu M, Kant AM, et al. (1999). "Cbl functions downstream of Src kinases in Fc gamma RI signaling in primary human macrophages.". J. Leukoc. Biol. 65 (4): 523–34. PMID 10204582. 
  • Asada H, Ishii N, Sasaki Y, et al. (1999). "Grf40, A novel Grb2 family member, is involved in T cell signaling through interaction with SLP-76 and LAT.". J. Exp. Med. 189 (9): 1383–90. doi:10.1084/jem.189.9.1383. PMID 10224278. 
  • Wunderlich L, Faragó A, Downward J, Buday L (1999). "Association of Nck with tyrosine-phosphorylated SLP-76 in activated T lymphocytes.". Eur. J. Immunol. 29 (4): 1068–75. doi:10.1002/(SICI)1521-4141(199904)29:04<1068::AID-IMMU1068>3.0.CO;2-P. PMID 10229072. 
  • Gross BS, Melford SK, Watson SP (1999). "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. doi:10.1046/j.1432-1327.1999.00560.x. PMID 10469124. 

[edit] See also

[edit] External links

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