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-transducingadaptor protein.[5]
Structure
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.
Function
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.[5] SLP-76 might serve as an integration point for signals by activating NK cell receptors.[6] In NK cells, SLP-76 can be phosphorylated by SYK or ZAP70 following ligation of activating receptors.[7]
Interactions
Lymphocyte cytosolic protein 2 has been shown to interact with:
^Park RK, Izadi KD, Deo YM, Durden DL (September 1999). "Role of Src in the modulation of multiple adaptor proteins in FcalphaRI oxidant signaling". Blood. 94 (6): 2112–2120. PMID10477741.
^ abErdreich-Epstein A, Liu M, Kant AM, Izadi KD, Nolta JA, Durden DL (April 1999). "Cbl functions downstream of Src kinases in Fc gamma RI signaling in primary human macrophages". J. Leukoc. Biol. 65 (4): 523–534. doi:10.1002/jlb.65.4.523. PMID10204582.
^Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–1178. doi:10.1038/nature04209. PMID16189514.
^Liu SK, Fang N, Koretzky GA, McGlade CJ (January 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. PMID10021361.
^Robinson A, Gibbins J, Rodríguez-Liñares B, Finan PM, Wilson L, Kellie S, Findell P, Watson SP (July 1996). "Characterization of Grb2-binding proteins in human platelets activated by Fc gamma RIIA cross-linking". Blood. 88 (2): 522–530. PMID8695800.
^ abcShim EK, Moon CS, Lee GY, Ha YJ, Chae SK, Lee JR (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. 575 (1–3): 35–40. doi:10.1016/j.febslet.2004.07.090. PMID15388330.
^Lindholm CK, Henriksson ML, Hallberg B, Welsh M (July 2002). "Shb links SLP-76 and Vav with the CD3 complex in Jurkat T cells". Eur. J. Biochem. 269 (13): 3279–3288. doi:10.1046/j.1432-1033.2002.03008.x. PMID12084069.
^Raab M, da Silva AJ, Findell PR, Rudd CE (February 1997). "Regulation of Vav-SLP-76 binding by ZAP-70 and its relevance to TCR zeta/CD3 induction of interleukin-2". Immunity. 6 (2): 155–164. doi:10.1016/S1074-7613(00)80422-7. PMID9047237.
Sunden SL, Carr LL, Clements JL, Motto DG, Koretzky GA (1996). "Polymorphism in and localization of the gene LCP2 (SLP-76) to chromosome 5q33.1-qter". Genomics. 35 (1): 269–270. doi:10.1006/geno.1996.0354. PMID8661136.
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): 155–164. doi:10.1016/S1074-7613(00)80422-7. PMID9047237.
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. PMID10021361.
Erdreich-Epstein A, Liu M, Kant AM, Izadi KD, Nolta JA, Durden DL (1999). "Cbl functions downstream of Src kinases in Fc gamma RI signaling in primary human macrophages". J. Leukoc. Biol. 65 (4): 523–534. doi:10.1002/jlb.65.4.523. PMID10204582.
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): 612–623. doi:10.1046/j.1432-1327.1999.00560.x. PMID10469124.