Lymphocyte cytosolic protein 2
| LCP2 | |||
|---|---|---|---|
Gene ontology | |||
| Molecular function | |||
| Cellular component | |||
| Biological process | |||
| Sources:Amigo / QuickGO | |||
Ensembl | |||||||||
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| UniProt | |||||||||
| RefSeq (mRNA) | |||||||||
| RefSeq (protein) | |||||||||
| Location (UCSC) | Chr 5: 170.25 – 170.3 Mb | Chr 11: 34 – 34.04 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| 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
natural killer cells.[8]
Structure and function
The amino acid sequence of the protein has a central domain with a high concentration of prolines, as well as domains at the amino-terminal and carboxy-terminal of the amino acid sequence. The PDB file 1H3H depicts the
ZAP-70, a tyrosine kinase. Along with the LAT (linker for activation of T cells) adaptor protein, SLP-76 is essential to nearly all downstream effects from T-cell receptor signals. SLP-76, LAT, and Gads together combine into protein complexes, typically with LAT at the center and SLP-76 proteins on the outside. These complexes associate into larger microclusters that activate a multitude of signaling pathways.[9][10] The proteins that bind SLP-76 are essential to the production and secretion of interleukin 2 (IL-2) and rearrangement of the actin cytoskeleton in T-cells, which is an important part of T-cell division and proliferation.[6]
Studies using SLP-76-deficient T cell lines or mice have provided strong evidence that SLP-76 plays a positive role more generally in promoting T cell development and activation, as well as mast cell and platelet function. SLP-76 is critical in the signaling from the pre-TCR that shifts T-cell developing thymocytes from the double-negative (DN) stage to the double-positive (DP) stage. Allelic exclusion of the second locus of the TCRβ chain is also dependent on signaling from the TCRβ chain that is first expressed, involving SLP-76 as a key intermediate.[6]
SLP-76 is also important in natural killer (NK) cells, in the signaling pathways of the NK cell receptors (NKRs). The SH2 domain on the C-terminus binds HPK-1, a serine-threonine kinase, and the adhesion and degranulation-promoting adaptor protein (ADAP) also known as FYB. Both these proteins are common to regular T-cells as well, but have unique downstream signaling effects in NK cells relating to their distribution across different tissues. Studies using mutations in the SH2 domain of mice show that it produces an accumulation of invariant NK cells in primary lymphoid organs like the thymus and in peripheral lymph nodes, with a simultaneous reduction of these cells in the livers and spleens.[11]
Interactions
Lymphocyte cytosolic protein 2 has been shown to
interact
with:
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000043462 - Ensembl, May 2017
- ^ a b c 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.
- ^ a b "Entrez Gene: LCP2 lymphocyte cytosolic protein 2 (SH2 domain containing leukocyte protein of 76kDa)".
- ^ PMID 10712938.
- ^ PMID 11680012.
- PMID 22786724.
- PMID 31402911.
- PMID 33575254.
- PMID 31293596.
- PMID 10477741.
- ^ S2CID 18340540.
- S2CID 4427026.
- PMID 10820259.
- S2CID 14131281.
- ^ PMID 10224278.
- PMID 11314042.
- PMID 8695800.
- PMID 8995445.
- ^ S2CID 24678709.
- PMID 10636929.
- PMID 10026222.
- PMID 10229072.
- PMID 11390650.
- PMID 9765283.
- PMID 8760799.
- PMID 12084069.
- PMID 9047237.
- PMID 8703037.
Further reading
- Jackman JK, Motto DG, Sun Q, Tanemoto M, Turck CW, Peltz GA, et al. (March 1995). "Molecular cloning of SLP-76, a 76-kDa tyrosine phosphoprotein associated with Grb2 in T cells". The Journal of Biological Chemistry. 270 (13): 7029–7032. PMID 7706237.
- Sunden SL, Carr LL, Clements JL, Motto DG, Koretzky GA (July 1996). "Polymorphism in and localization of the gene LCP2 (SLP-76) to chromosome 5q33.1-qter". Genomics. 35 (1): 269–270. PMID 8661136.
- Motto DG, Ross SE, Wu J, Hendricks-Taylor LR, Koretzky GA (April 1996). "Implication of the GRB2-associated phosphoprotein SLP-76 in T cell receptor-mediated interleukin 2 production". The Journal of Experimental Medicine. 183 (4): 1937–1943. PMID 8666952.
- Bubeck Wardenburg J, Fu C, Jackman JK, Flotow H, Wilkinson SE, Williams DH, et al. (August 1996). "Phosphorylation of SLP-76 by the ZAP-70 protein-tyrosine kinase is required for T-cell receptor function". The Journal of Biological Chemistry. 271 (33): 19641–19644. PMID 8702662.
- 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". The Journal of Biological Chemistry. 271 (36): 22225–22230. PMID 8703037.
- 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". The Journal of Experimental Medicine. 184 (2): 457–463. PMID 8760799.
- 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. PMID 9047237.
- Musci MA, Hendricks-Taylor LR, Motto DG, Paskind M, Kamens J, Turck CW, Koretzky GA (May 1997). "Molecular cloning of SLAP-130, an SLP-76-associated substrate of the T cell antigen receptor-stimulated protein tyrosine kinases". The Journal of Biological Chemistry. 272 (18): 11674–11677. PMID 9115214.
- da Silva AJ, Li Z, de Vera C, Canto E, Findell P, Rudd CE (July 1997). "Cloning of a novel T-cell protein FYB that binds FYN and SH2-domain-containing leukocyte protein 76 and modulates interleukin 2 production". Proceedings of the National Academy of Sciences of the United States of America. 94 (14): 7493–7498. PMID 9207119.
- Fu C, Chan AC (October 1997). "Identification of two tyrosine phosphoproteins, pp70 and pp68, which interact with phospholipase Cgamma, Grb2, and Vav after B cell antigen receptor activation". The Journal of Biological Chemistry. 272 (43): 27362–27368. PMID 9341187.
- Zhang W, Sloan-Lancaster J, Kitchen J, Trible RP, Samelson LE (January 1998). "LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation". Cell. 92 (1): 83–92. S2CID 1806525.
- Fu C, Turck CW, Kurosaki T, Chan AC (July 1998). "BLNK: a central linker protein in B cell activation". Immunity. 9 (1): 93–103. PMID 9697839.
- Chu J, Liu Y, Koretzky GA, Durden DL (September 1998). "SLP-76-Cbl-Grb2-Shc interactions in FcgammaRI signaling". Blood. 92 (5): 1697–1706. PMID 9716598.
- Binstadt BA, Billadeau DD, Jevremović D, Williams BL, Fang N, Yi T, et al. (October 1998). "SLP-76 is a direct substrate of SHP-1 recruited to killer cell inhibitory receptors". The Journal of Biological Chemistry. 273 (42): 27518–27523. PMID 9765283.
- 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". Current Biology. 9 (2): 67–75. S2CID 14131281.
- Gross BS, Lee JR, Clements JL, Turner M, Tybulewicz VL, Findell PR, et al. (February 1999). "Tyrosine phosphorylation of SLP-76 is downstream of Syk following stimulation of the collagen receptor in platelets". The Journal of Biological Chemistry. 274 (9): 5963–5971. PMID 10026222.
- 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". Journal of Leukocyte Biology. 65 (4): 523–534. S2CID 18340540.
- Asada H, Ishii N, Sasaki Y, Endo K, Kasai H, Tanaka N, et al. (May 1999). "Grf40, A novel Grb2 family member, is involved in T cell signaling through interaction with SLP-76 and LAT". The Journal of Experimental Medicine. 189 (9): 1383–1390. PMID 10224278.
- Wunderlich L, Faragó A, Downward J, Buday L (April 1999). "Association of Nck with tyrosine-phosphorylated SLP-76 in activated T lymphocytes". European Journal of Immunology. 29 (4): 1068–1075. PMID 10229072.
- Gross BS, Melford SK, Watson SP (August 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". European Journal of Biochemistry. 263 (3): 612–623. PMID 10469124.
External links
- SLP-76+signal+Transducing+adaptor+proteins at the U.S. National Library of Medicine Medical Subject Headings (MeSH)