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0  structures 25  species 0  interactions 45  sequences 2  architectures

Family: LAT (PF15234)

Summary: Linker for activation of T-cells

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This is the Wikipedia entry entitled "Linker of activated T cells". More...

Linker of activated T cells Edit Wikipedia article

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

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 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". 
  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

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

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Linker for activation of T-cells Provide feedback

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Literature references

  1. Sommers CL, Samelson LE, Love PE;, Bioessays. 2004;26:61-67.: LAT: a T lymphocyte adapter protein that couples the antigen receptor to downstream signaling pathways. PUBMED:14696041 EPMC:14696041


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Representative proteomes NCBI
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RP15
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RP35
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RP55
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RP75
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Seed source: Jackhmmer:O43561
Previous IDs: none
Type: Family
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 %

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build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 27.0 27.0
Trusted cut-off 28.9 36.5
Noise cut-off 23.7 23.7
Model length: 230
Family (HMM) version: 1
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