Linker of activated T cells

Linker for activation of T cells
Identifiers
Symbols LAT; LAT1; pp36
External IDs OMIM: 602354 MGI: 1342293 HomoloGene: 7811 GeneCards: LAT Gene
Orthologs
Species Human Mouse
Entrez 27040 16797
Ensembl ENSG00000213658 ENSMUSG00000030742
UniProt O43561 Q546H1
RefSeq (mRNA) NM_001014987.1 NM_010689.2
RefSeq (protein) NP_001014987.1 NP_034819.1
Location (UCSC) Chr 16:
29 – 29 Mb		 Chr 7:
133.51 – 133.51 Mb
PubMed search [1] [2]

Linker of Activated 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]

Contents

Function

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

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

Linker of activated 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

  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". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27040. 
  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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=358815. 
  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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2212210. 
  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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1221857. 
  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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2193052. 
  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

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