Lymphocyte cytosolic protein 2

LCP2
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1H3H, 1YWO, 2EAP, 2ROR
Identifiers
Aliases	LCP2, SLP-76, SLP76, lymphocyte cytosolic protein 2
External IDs	OMIM: 601603 MGI: 1321402 HomoloGene: 4065 GeneCards: LCP2
Gene location (Human)
Chr.	Chromosome 5 (human)[1]
End	170,297,818 bp[1]
Gene location (Mouse)
Chr.	Chromosome 11 (mouse)[2]
End	34,092,295 bp[2]
RNA expression pattern
	; ;
	More reference expression data
Gene ontology
Molecular function	• GO:0001948 protein binding;
Cellular component	• cytoplasm; • cytosol; • TCR signalosome; • intercellular junction; • plasma membrane raft;
Biological process	• platelet activation; • mast cell activation; • Fc-epsilon receptor signaling pathway; • positive regulation of protein kinase activity; • cytokine secretion; • GO:0007243 intracellular signal transduction; • T cell receptor signaling pathway; • immune response; • transmembrane receptor protein tyrosine kinase signaling pathway;
	Sources:Amigo / QuickGO
Orthologs
	3937
	16822
	ENSG00000043462
	ENSMUSG00000002699
	Q13094
	Q60787
	NM_005565
	NM_010696
	NP_005556
	NP_034826
	Wikidata
View/Edit Human	View/Edit Mouse

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.[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:

Cbl gene,[8][9]
GRAP2,[10][11][12][13]
Grb2,[9][13][14][15][16]
ITK[17][18]
LYN,[19]
NCK1,[17][20]
PIK3R1,[17]
PLCG1,[21]
PTPN6,[22][23]
SHB,[24] and
VAV1.[25][26]

References

GRCh38: Ensembl release 89: ENSG00000043462 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000002699 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Entrez Gene: LCP2 lymphocyte cytosolic protein 2 (SH2 domain containing leukocyte protein of 76kDa)".
Kim, Hun Sik; Long, Eric O. (2012-07-10). "Complementary Phosphorylation Sites in the Adaptor Protein SLP-76 Promote Synergistic Activation of Natural Killer Cells". Science Signaling. 5 (232): ra49. doi:10.1126/scisignal.2002754. ISSN 1937-9145. PMC 3842037. PMID 22786724.
Fasbender, Frank; Claus, Maren; Wingert, Sabine; Sandusky, Mina; Watzl, Carsten (2017-07-07). "Differential Requirements for Src-Family Kinases in SYK or ZAP70-Mediated SLP-76 Phosphorylation in Lymphocytes". Frontiers in Immunology. 8: 789. doi:10.3389/fimmu.2017.00789. ISSN 1664-3224. PMC 5500614. PMID 28736554.
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. doi:10.1182/blood.V94.6.2112. PMID 10477741.
Erdreich-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. PMID 10204582. S2CID 18340540.
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. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
Ellis JH, Ashman C, Burden MN, Kilpatrick KE, Morse MA, Hamblin PA (June 2000). "GRID: a novel Grb-2-related adapter protein that interacts with the activated T cell costimulatory receptor CD28". J. Immunol. 164 (11): 5805–5814. doi:10.4049/jimmunol.164.11.5805. PMID 10820259.
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. PMID 10021361. S2CID 14131281.
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. 189 (9): 1383–1390. doi:10.1084/jem.189.9.1383. PMC 2193052. PMID 10224278.
Lewitzky M, Kardinal C, Gehring NH, Schmidt EK, Konkol B, Eulitz M, Birchmeier W, Schaeper U, Feller SM (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. 20 (9): 1052–1062. doi:10.1038/sj.onc.1204202. PMID 11314042.
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. doi:10.1182/blood.V88.2.522.bloodjournal882522. PMID 8695800.
Hendricks-Taylor LR, Motto DG, Zhang J, Siraganian RP, Koretzky GA (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. 272 (2): 1363–1367. doi:10.1074/jbc.272.2.1363. PMID 8995445.
Shim 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. PMID 15388330. S2CID 24678709.
Bunnell SC, Diehn M, Yaffe MB, Findell PR, Cantley LC, Berg LJ (January 2000). "Biochemical interactions integrating Itk with the T cell receptor-initiated signaling cascade". J. Biol. Chem. 275 (3): 2219–2230. doi:10.1074/jbc.275.3.2219. PMID 10636929.
Gross BS, Lee JR, Clements JL, Turner M, Tybulewicz VL, Findell PR, Koretzky GA, Watson SP (February 1999). "Tyrosine phosphorylation of SLP-76 is downstream of Syk following stimulation of the collagen receptor in platelets". J. Biol. Chem. 274 (9): 5963–5971. doi:10.1074/jbc.274.9.5963. PMID 10026222.
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. 29 (4): 1068–1075. doi:10.1002/(SICI)1521-4141(199904)29:04<1068::AID-IMMU1068>3.0.CO;2-P. PMID 10229072.
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. 21 (13): 4208–4218. doi:10.1128/MCB.21.13.4208-4218.2001. PMC 87082. PMID 11390650.
Binstadt BA, Billadeau DD, Jevremović D, Williams BL, Fang N, Yi T, Koretzky GA, Abraham RT, Leibson PJ (October 1998). "SLP-76 is a direct substrate of SHP-1 recruited to killer cell inhibitory receptors". J. Biol. Chem. 273 (42): 27518–27523. doi:10.1074/jbc.273.42.27518. PMID 9765283.
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. 184 (2): 457–463. doi:10.1084/jem.184.2.457. PMC 2192711. PMID 8760799.
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. PMID 12084069.
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. PMID 9047237.
Onodera H, Motto DG, Koretzky GA, Rothstein DM (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. 271 (36): 22225–22230. doi:10.1074/jbc.271.36.22225. PMID 8703037.

External links

SLP-76+signal+Transducing+adaptor+proteins at the US National Library of Medicine Medical Subject Headings (MeSH)

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000043462 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000002699 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-5] "Entrez Gene: LCP2 lymphocyte cytosolic protein 2 (SH2 domain containing leukocyte protein of 76kDa)".

[6] Kim, Hun Sik; Long, Eric O. (2012-07-10). "Complementary Phosphorylation Sites in the Adaptor Protein SLP-76 Promote Synergistic Activation of Natural Killer Cells". Science Signaling. 5 (232): ra49. doi:10.1126/scisignal.2002754. ISSN 1937-9145. PMC 3842037. PMID 22786724.

[7] Fasbender, Frank; Claus, Maren; Wingert, Sabine; Sandusky, Mina; Watzl, Carsten (2017-07-07). "Differential Requirements for Src-Family Kinases in SYK or ZAP70-Mediated SLP-76 Phosphorylation in Lymphocytes". Frontiers in Immunology. 8: 789. doi:10.3389/fimmu.2017.00789. ISSN 1664-3224. PMC 5500614. PMID 28736554.

[pmid10477741-8] 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. doi:10.1182/blood.V94.6.2112. PMID 10477741.

[pmid10204582-9] Erdreich-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. PMID 10204582. S2CID 18340540.

[pmid16189514-10] 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. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.

[pmid10820259-11] Ellis JH, Ashman C, Burden MN, Kilpatrick KE, Morse MA, Hamblin PA (June 2000). "GRID: a novel Grb-2-related adapter protein that interacts with the activated T cell costimulatory receptor CD28". J. Immunol. 164 (11): 5805–5814. doi:10.4049/jimmunol.164.11.5805. PMID 10820259.

[pmid10021361-12] 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. PMID 10021361. S2CID 14131281.

[pmid10224278-13] 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. 189 (9): 1383–1390. doi:10.1084/jem.189.9.1383. PMC 2193052. PMID 10224278.

[pmid11314042-14] Lewitzky M, Kardinal C, Gehring NH, Schmidt EK, Konkol B, Eulitz M, Birchmeier W, Schaeper U, Feller SM (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. 20 (9): 1052–1062. doi:10.1038/sj.onc.1204202. PMID 11314042.

[pmid8695800-15] 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. doi:10.1182/blood.V88.2.522.bloodjournal882522. PMID 8695800.

[pmid8995445-16] Hendricks-Taylor LR, Motto DG, Zhang J, Siraganian RP, Koretzky GA (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. 272 (2): 1363–1367. doi:10.1074/jbc.272.2.1363. PMID 8995445.

[pmid15388330-17] Shim 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. PMID 15388330. S2CID 24678709.

[pmid10636929-18] Bunnell SC, Diehn M, Yaffe MB, Findell PR, Cantley LC, Berg LJ (January 2000). "Biochemical interactions integrating Itk with the T cell receptor-initiated signaling cascade". J. Biol. Chem. 275 (3): 2219–2230. doi:10.1074/jbc.275.3.2219. PMID 10636929.

[pmid10026222-19] Gross BS, Lee JR, Clements JL, Turner M, Tybulewicz VL, Findell PR, Koretzky GA, Watson SP (February 1999). "Tyrosine phosphorylation of SLP-76 is downstream of Syk following stimulation of the collagen receptor in platelets". J. Biol. Chem. 274 (9): 5963–5971. doi:10.1074/jbc.274.9.5963. PMID 10026222.

[pmid10229072-20] 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. 29 (4): 1068–1075. doi:10.1002/(SICI)1521-4141(199904)29:04<1068::AID-IMMU1068>3.0.CO;2-P. PMID 10229072.

[pmid11390650-21] 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. 21 (13): 4208–4218. doi:10.1128/MCB.21.13.4208-4218.2001. PMC 87082. PMID 11390650.

[pmid9765283-22] Binstadt BA, Billadeau DD, Jevremović D, Williams BL, Fang N, Yi T, Koretzky GA, Abraham RT, Leibson PJ (October 1998). "SLP-76 is a direct substrate of SHP-1 recruited to killer cell inhibitory receptors". J. Biol. Chem. 273 (42): 27518–27523. doi:10.1074/jbc.273.42.27518. PMID 9765283.

[pmid8760799-23] 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. 184 (2): 457–463. doi:10.1084/jem.184.2.457. PMC 2192711. PMID 8760799.

[pmid12084069-24] 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. PMID 12084069.

[pmid9047237-25] 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. PMID 9047237.

[pmid8703037-26] Onodera H, Motto DG, Koretzky GA, Rothstein DM (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. 271 (36): 22225–22230. doi:10.1074/jbc.271.36.22225. PMID 8703037.