Linker of activated T cells

From Wikipedia, the free encyclopedia
  (Redirected from Linker of Activated T cells)
Jump to: navigation, search
Linker for activation of T cells
Identifiers
Symbols LAT ; LAT1; pp36
External IDs OMIM602354 MGI1342293 HomoloGene7811 ChEMBL: 5779 GeneCards: LAT Gene
Orthologs
Species Human Mouse
Entrez 27040 16797
Ensembl ENSG00000213658 ENSMUSG00000030742
UniProt O43561 O54957
RefSeq (mRNA) NM_001014987 NM_010689
RefSeq (protein) NP_001014987 NP_034819
Location (UCSC) Chr 16:
29 – 29 Mb
Chr 7:
126.36 – 126.37 Mb
PubMed search [1] [2]

The Linker for Activation of T cells, also known as LAT, is a protein which in humans is encoded by the LAT gene.[1] Alternative splicing results in multiple transcript variants encoding different isoforms.[2]

Function[edit]

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.[3] Upon phosphorylation, this protein recruits multiple adaptor proteins and downstream signaling molecules into multimolecular signaling complexes located near the site of TCR engagement.[2]

Discovery[edit]

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.[4] 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.[1][5]

Interactions[edit]

The Linker for Activation of T cells has been shown to interact with SHB,[6][7] PLCG1,[1][8][9] GRAP2,[10][11] ZAP-70,[9][12] GRAP,[1][12] Grb2,[1][9][12] PIK3R1,[9] ITK,[12][13] MAP4K1[14] and VAV1.[9][12]

References[edit]

  1. ^ a b c d e 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. 
  2. ^ a b "Entrez Gene: LAT Linker of Activated T cells". 
  3. ^ 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. 
  4. ^ 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. 
  5. ^ 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. 
  6. ^ 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. 
  7. ^ 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. 
  8. ^ 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. 
  9. ^ a b c d e 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. 
  10. ^ 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. 
  11. ^ 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. 
  12. ^ a b c d e 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. 
  13. ^ 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. 
  14. ^ 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. 

Further reading[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.