Summary: Linker for activation of T-cells
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Linker of activated T cells Edit Wikipedia article
|Linker for activation of T cells|
|External IDs||ChEMBL: GeneCards:|
The Linker for Activation of T cells, also known as LAT, is a protein which in humans is encoded by the LAT gene. Alternative splicing results in multiple transcript variants encoding different isoforms.
The protein encoded by this gene is phosphorylated by ZAP70/Syk protein tyrosine kinases following activation of the T-cell antigen receptor (TCR) signal transduction pathway. This transmembrane protein localizes to lipid rafts (also known as glycosphingolipid-enriched microdomains or GEMs) and acts as a docking site for SH2 domain-containing proteins. Upon phosphorylation, this protein recruits multiple adaptor proteins and downstream signaling molecules into multimolecular signaling complexes located near the site of TCR engagement.
LAT was described in the early 1990s as a phosphoprotein of 36–38 kDa (pp. 36–38) rapidly phosphorylated on tyrosine residues following TCR ligation. Cloning of the gene revealed that the protein product is a type III (leaderless) transmembrane protein of 262 aminoacids (long form) or 233 aminoacids (short form) in humans, 242 aminoacids in mouse, and 241 aminoacids in rat.
The Linker for Activation of T cells has been shown to interact with SHB, PLCG1, GRAP2, ZAP-70, GRAP, Grb2, PIK3R1, ITK, MAP4K1 and VAV1.
- 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. doi:10.1016/S0092-8674(00)80901-0. PMID 9489702.
- "Entrez Gene: LAT Linker of Activated T cells".
- Horejsí V (2004). "Transmembrane adaptor proteins in membrane microdomains: important regulators of immunoreceptor signaling". Immunol. Lett. 92 (1–2): 43–9. doi:10.1016/j.imlet.2003.10.013. PMID 15081526.
- Sieh M, Batzer A, Schlessinger J, Weiss A (1994). "GRB2 and phospholipase C-gamma 1 associate with a 36- to 38-kilodalton phosphotyrosine protein after T-cell receptor stimulation". Mol. Cell. Biol. 14 (7): 4435–42. PMC 358815. PMID 7516467.
- Weber JR, Orstavik S, Torgersen KM, Danbolt NC, Berg SF, Ryan JC, Taskén K, Imboden JB, Vaage JT (1998). "Molecular Cloning of the cDNA Encoding pp36, a Tyrosine-phosphorylated Adaptor Protein Selectively Expressed by T Cells and Natural Killer Cells". J. Exp. Med. 187 (7): 1157–61. doi:10.1084/jem.187.7.1157. PMC 2212210. PMID 9529333.
- Lindholm, C K; Gylfe E, Zhang W, Samelson L E, Welsh M (Sep 1999). "Requirement of the Src homology 2 domain protein Shb for T cell receptor-dependent activation of the interleukin-2 gene nuclear factor for activation of T cells element in Jurkat T cells". J. Biol. Chem. (UNITED STATES) 274 (39): 28050–7. doi:10.1074/jbc.274.39.28050. ISSN 0021-9258. PMID 10488157.
- 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. doi:10.1046/j.1432-1033.2002.03008.x. ISSN 0014-2956. PMID 12084069.
- Zhang, W; Trible R P, Samelson L E (Aug 1998). "LAT palmitoylation: its essential role in membrane microdomain targeting and tyrosine phosphorylation during T cell activation". Immunity (UNITED STATES) 9 (2): 239–46. doi:10.1016/S1074-7613(00)80606-8. ISSN 1074-7613. PMID 9729044.
- Paz, P E; Wang S, Clarke H, Lu X, Stokoe D, Abo A (Jun 2001). "Mapping the Zap-70 phosphorylation sites on LAT (linker for activation of T cells) required for recruitment and activation of signalling proteins in T cells". Biochem. J. (England) 356 (Pt 2): 461–71. doi:10.1042/0264-6021:3560461. ISSN 0264-6021. PMC 1221857. PMID 11368773.
- 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. doi:10.1016/S0960-9822(99)80017-7. ISSN 0960-9822. PMID 10021361.
- 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.
- Perez-Villar, Juan J; Whitney Gena S, Sitnick Mitchell T, Dunn Robert J, Venkatesan Srividhya, O'Day Kathleen, Schieven Gary L, Lin Tai-An, Kanner Steven B (Aug 2002). "Phosphorylation of the linker for activation of T-cells by Itk promotes recruitment of Vav". Biochemistry (United States) 41 (34): 10732–40. doi:10.1021/bi025554o. ISSN 0006-2960. PMID 12186560.
- Shan, X; Wange R L (Oct 1999). "Itk/Emt/Tsk activation in response to CD3 cross-linking in Jurkat T cells requires ZAP-70 and Lat and is independent of membrane recruitment". J. Biol. Chem. (UNITED STATES) 274 (41): 29323–30. doi:10.1074/jbc.274.41.29323. ISSN 0021-9258. PMID 10506192.
- Ling, P; Meyer C F, Redmond L P, Shui J W, Davis B, Rich R R, Hu M C, Wange R L, Tan T H (Jun 2001). "Involvement of hematopoietic progenitor kinase 1 in T cell receptor signaling". J. Biol. Chem. (United States) 276 (22): 18908–14. doi:10.1074/jbc.M101485200. ISSN 0021-9258. PMID 11279207.
- Wange RL (2002). "LAT, the linker for activation of T cells: a bridge between T cell-specific and general signaling pathways". Sci. STKE 2000 (63): RE1. doi:10.1126/stke.2000.63.re1. PMID 11752630.
- Sommers CL, Samelson LE, Love PE (2004). "LAT: a T lymphocyte adapter protein that couples the antigen receptor to downstream signaling pathways". Bioessays 26 (1): 61–7. doi:10.1002/bies.10384. PMID 14696041.
- Rivera J (2005). "NTAL/LAB and LAT: a balancing act in mast-cell activation and function". Trends Immunol. 26 (3): 119–22. doi:10.1016/j.it.2005.01.001. PMID 15745852.
- Trüb T, Frantz JD, Miyazaki M et al. (1997). "The role of a lymphoid-restricted, Grb2-like SH3-SH2-SH3 protein in T cell receptor signaling". J. Biol. Chem. 272 (2): 894–902. doi:10.1074/jbc.272.2.894. PMID 8995379.
- Hendricks-Taylor LR, Motto DG, Zhang J et al. (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): 1363–7. doi:10.1074/jbc.272.2.1363. PMID 8995445.
- 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.
- Weber JR, Orstavik S, Torgersen KM et al. (1998). "Molecular Cloning of the cDNA Encoding pp36, a Tyrosine-phosphorylated Adaptor Protein Selectively Expressed by T Cells and Natural Killer Cells". J. Exp. Med. 187 (7): 1157–61. doi:10.1084/jem.187.7.1157. PMC 2212210. PMID 9529333.
- Zhang W, Trible RP, Samelson LE (1998). "LAT palmitoylation: its essential role in membrane microdomain targeting and tyrosine phosphorylation during T cell activation". Immunity 9 (2): 239–46. doi:10.1016/S1074-7613(00)80606-8. PMID 9729044.
- Finco TS, Kadlecek T, Zhang W et al. (1998). "LAT is required for TCR-mediated activation of PLCgamma1 and the Ras pathway". Immunity 9 (5): 617–26. doi:10.1016/S1074-7613(00)80659-7. PMID 9846483.
- Sarkar S (1999). "Tyrosine phosphorylation and translocation of LAT in platelets". FEBS Lett. 441 (3): 357–60. doi:10.1016/S0014-5793(98)01584-1. PMID 9891970.
- 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.
- Jevremovic D, Billadeau DD, Schoon RA et al. (1999). "Cutting edge: a role for the adaptor protein LAT in human NK cell-mediated cytotoxicity". J. Immunol. 162 (5): 2453–6. PMID 10072481.
- Zhang W, Sommers CL, Burshtyn DN et al. (1999). "Essential role of LAT in T cell development". Immunity 10 (3): 323–32. doi:10.1016/S1074-7613(00)80032-1. PMID 10204488.
- Tang J, Sawasdikosol S, Chang JH, Burakoff SJ (1999). "SLAP, a dimeric adapter protein, plays a functional role in T cell receptor signaling". Proc. Natl. Acad. Sci. U.S.A. 96 (17): 9775–80. doi:10.1073/pnas.96.17.9775. PMC 22286. PMID 10449770.
- 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.
- Lindholm CK, Gylfe E, Zhang W et al. (1999). "Requirement of the Src homology 2 domain protein Shb for T cell receptor-dependent activation of the interleukin-2 gene nuclear factor for activation of T cells element in Jurkat T cells". J. Biol. Chem. 274 (39): 28050–7. doi:10.1074/jbc.274.39.28050. PMID 10488157.
- Shan X, Wange RL (1999). "Itk/Emt/Tsk activation in response to CD3 cross-linking in Jurkat T cells requires ZAP-70 and Lat and is independent of membrane recruitment". J. Biol. Chem. 274 (41): 29323–30. doi:10.1074/jbc.274.41.29323. PMID 10506192.
- Bosselut R, Zhang W, Ashe JM et al. (1999). "Association of the Adaptor Molecule Lat with Cd4 and Cd8 Coreceptors Identifies a New Coreceptor Function in T Cell Receptor Signal Transduction". J. Exp. Med. 190 (10): 1517–26. doi:10.1084/jem.190.10.1517. PMC 2195704. PMID 10562325.
- Tridandapani S, Lyden TW, Smith JL et al. (2000). "The adapter protein LAT enhances fcgamma receptor-mediated signal transduction in myeloid cells". J. Biol. Chem. 275 (27): 20480–7. doi:10.1074/jbc.M909462199. PMID 10781611.
- Zhang W, Trible RP, Zhu M et al. (2000). "Association of Grb2, Gads, and phospholipase C-gamma 1 with phosphorylated LAT tyrosine residues. Effect of LAT tyrosine mutations on T cell angigen receptor-mediated signaling". J. Biol. Chem. 275 (30): 23355–61. doi:10.1074/jbc.M000404200. PMID 10811803.
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|Author:||Eberhardt RY, Coggill P, Hetherington K|
|Number in seed:||10|
|Number in full:||45|
|Average length of the domain:||221.60 aa|
|Average identity of full alignment:||68 %|
|Average coverage of the sequence by the domain:||95.17 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||1|
|Download:||download the raw HMM for this family|
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For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
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