Linker for Activation of T cells

LAT
Identifiers
AliasesLAT, Lat, LAT1, pp36, linker for activation of T-cells, IMD52
External IDsMGI: 1342293 HomoloGene: 7811 GeneCards: LAT
Gene location (Human)
Chr.Chromosome 16 (human)[1]
BandNo data availableStart28,984,826 bp[1]
End28,990,783 bp[1]
Orthologs
SpeciesHumanMouse
Entrez

27040

16797

Ensembl

ENSG00000213658

ENSMUSG00000030742

UniProt

O43561

O54957

RefSeq (mRNA)

NM_001014987
NM_001014988
NM_001014989
NM_014387

NM_010689

RefSeq (protein)

NP_001014987
NP_001014988
NP_001014989
NP_055202

NP_034819

Location (UCSC)Chr 16: 28.98 – 28.99 MbChr 16: 126.36 – 126.37 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[5] Alternative splicing results in multiple transcript variants encoding different isoforms.[6]

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.[7] Upon phosphorylation, this protein recruits multiple adaptor proteins and downstream signaling molecules into multimolecular signaling complexes located near the site of TCR engagement.[6]

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.[8] 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.[5][9]

Interactions

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

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000213658 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000030742 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:".
  4. ↑ "Mouse PubMed Reference:".
  5. 1 2 3 4 5 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. PMID 9489702. doi:10.1016/S0092-8674(00)80901-0.
  6. 1 2 "Entrez Gene: LAT Linker of Activated T cells".
  7. ↑ Horejsí V (2004). "Transmembrane adaptor proteins in membrane microdomains: important regulators of immunoreceptor signaling". Immunol. Lett. 92 (1–2): 43–9. PMID 15081526. doi:10.1016/j.imlet.2003.10.013.
  8. ↑ 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 Freely accessible. PMID 7516467.
  9. ↑ 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. PMC 2212210 Freely accessible. PMID 9529333. doi:10.1084/jem.187.7.1157.
  10. ↑ 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. PMID 10021361. doi:10.1016/S0960-9822(99)80017-7.
  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. 189 (9): 1383–90. PMC 2193052 Freely accessible. PMID 10224278. doi:10.1084/jem.189.9.1383.
  12. 1 2 3 4 5 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. PMID 12186560. doi:10.1021/bi025554o.
  13. 1 2 3 4 5 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. PMC 1221857 Freely accessible. PMID 11368773. doi:10.1042/0264-6021:3560461.
  14. ↑ 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. PMID 10506192. doi:10.1074/jbc.274.41.29323.
  15. ↑ 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. PMID 11279207. doi:10.1074/jbc.M101485200.
  16. ↑ 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. PMID 9729044. doi:10.1016/S1074-7613(00)80606-8.
  17. ↑ 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. PMID 10488157. doi:10.1074/jbc.274.39.28050.
  18. ↑ 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. PMID 12084069. doi:10.1046/j.1432-1033.2002.03008.x.

Further reading

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

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.