Linker for Activation of T cells

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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The Linker for Activation of T cells, also known as Linker of Activated T cells or 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

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

The Linker for Activation of T cells has been shown to interact with:

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 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. ↑ 2.0 2.1 "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. ↑ Liu SK, Fang N, Koretzky GA, McGlade CJ (Jan 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.
  7. ↑ 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): 1383–90. doi:10.1084/jem.189.9.1383. PMC 2193052. PMID 10224278.
  8. ↑ 8.0 8.1 8.2 8.3 8.4 Perez-Villar JJ, Whitney GS, Sitnick MT, Dunn RJ, Venkatesan S, O'Day K, Schieven GL, Lin TA, Kanner SB (Aug 2002). "Phosphorylation of the linker for activation of T-cells by Itk promotes recruitment of Vav". Biochemistry. 41 (34): 10732–40. doi:10.1021/bi025554o. PMID 12186560.
  9. ↑ 9.0 9.1 9.2 9.3 9.4 Paz PE, 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. 356 (Pt 2): 461–71. doi:10.1042/0264-6021:3560461. PMC 1221857. PMID 11368773.
  10. ↑ Shan X, Wange RL (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. 274 (41): 29323–30. doi:10.1074/jbc.274.41.29323. PMID 10506192.
  11. ↑ Ling P, Meyer CF, Redmond LP, Shui JW, Davis B, Rich RR, Hu MC, Wange RL, Tan TH (Jun 2001). "Involvement of hematopoietic progenitor kinase 1 in T cell receptor signaling". J. Biol. Chem. 276 (22): 18908–14. doi:10.1074/jbc.M101485200. PMID 11279207.
  12. ↑ Zhang W, Trible RP, Samelson LE (Aug 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.
  13. ↑ Lindholm CK, Gylfe E, Zhang W, Samelson LE, 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. 274 (39): 28050–7. doi:10.1074/jbc.274.39.28050. PMID 10488157.
  14. ↑ Lindholm CK, Henriksson ML, Hallberg B, Welsh M (Jul 2002). "Shb links SLP-76 and Vav with the CD3 complex in Jurkat T cells". Eur. J. Biochem. 269 (13): 3279–88. doi:10.1046/j.1432-1033.2002.03008.x. PMID 12084069.

Further reading

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

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