Lymphocyte cytosolic protein 2

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Lymphocyte cytosolic protein 2 (SH2 domain containing leukocyte protein of 76kDa)
PDB 1h3h EBI.jpg
Rendering of 1H3H
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols LCP2 ; SLP-76; SLP76
External IDs OMIM601603 MGI1321402 HomoloGene4065 GeneCards: LCP2 Gene
RNA expression pattern
PBB GE LCP2 205269 at tn.png
PBB GE LCP2 205270 s at tn.png
More reference expression data
Species Human Mouse
Entrez 3937 16822
Ensembl ENSG00000043462 ENSMUSG00000002699
UniProt Q13094 Q60787
RefSeq (mRNA) NM_005565 NM_010696
RefSeq (protein) NP_005556 NP_034826
Location (UCSC) Chr 5:
169.67 – 169.73 Mb
Chr 11:
34.05 – 34.09 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 that encodes a signal-transducing adaptor protein.[1]

No full structure for SLP-76 has been solved. The PDB file 1H3H depicts the SH3 domain of GRAP2 in complex with an RSTK-containing peptide representing residues 226-235 of SLP-76.

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 composed of three modular domains. The NH2-terminus contains an acidic region that includes a PEST domain and several tyrosine residues that 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]


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,[10][14][15][16][17] ITK[7][18] and VAV1.[19][20]

See also[edit]


  1. ^ a b "Entrez Gene: LCP2 lymphocyte cytosolic protein 2 (SH2 domain containing leukocyte protein of 76kDa)". 
  2. ^ Lindholm, Cecilia K; Henriksson Maria L; Hallberg Bengt; Welsh Michael (July 2002). "Shb links SLP-76 and Vav with the CD3 complex in Jurkat T cells". Eur. J. Biochem. (Germany) 269 (13): 3279–88. doi:10.1046/j.1432-1033.2002.03008.x. ISSN 0014-2956. PMID 12084069. 
  3. ^ 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. 
  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 (October 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. doi:10.1074/jbc.273.42.27518. ISSN 0021-9258. PMID 9765283. 
  5. ^ Mizuno, K; Katagiri T; Hasegawa K; Ogimoto M; Yakura H (August 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. doi:10.1084/jem.184.2.457. ISSN 0022-1007. PMC 2192711. 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 (February 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. doi:10.1074/jbc.274.9.5963. 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 (September 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 (April 1999). "Association of Nck with tyrosine-phosphorylated SLP-76 in activated T lymphocytes". Eur. J. Immunol. (GERMANY) 29 (4): 1068–75. doi:10.1002/(SICI)1521-4141(199904)29:04<1068::AID-IMMU1068>3.0.CO;2-P. ISSN 0014-2980. PMID 10229072. 
  9. ^ Park, R K; Izadi K D; Deo Y M; Durden D L (September 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 (April 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 (October 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 (June 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. doi:10.4049/jimmunol.164.11.5805. ISSN 0022-1767. PMID 10820259. 
  13. ^ Liu, S K; Fang N; Koretzky G A; McGlade C J (January 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. doi:10.1016/S0960-9822(99)80017-7. 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. doi:10.1084/jem.189.9.1383. ISSN 0022-1007. PMC 2193052. PMID 10224278. 
  15. ^ Lewitzky, M; Kardinal C; Gehring N H; Schmidt E K; Konkol B; Eulitz M; Birchmeier W; Schaeper U; Feller S M (March 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 (July 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 (January 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. doi:10.1074/jbc.272.2.1363. ISSN 0021-9258. PMID 8995445. 
  18. ^ Bunnell, S C; Diehn M; Yaffe M B; Findell P R; Cantley L C; Berg L J (January 2000). "Biochemical interactions integrating Itk with the T cell receptor-initiated signaling cascade". J. Biol. Chem. (UNITED STATES) 275 (3): 2219–30. doi:10.1074/jbc.275.3.2219. ISSN 0021-9258. PMID 10636929. 
  19. ^ Raab, M; da Silva A J; Findell P R; Rudd C E (February 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. doi:10.1016/S1074-7613(00)80422-7. ISSN 1074-7613. PMID 9047237. 
  20. ^ Onodera, H; Motto D G; Koretzky G A; Rothstein D M (September 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. doi:10.1074/jbc.271.36.22225. ISSN 0021-9258. PMID 8703037. 

Further reading[edit]

External links[edit]