The LAT protein encoded by the gene of the same name, plays a key role in the diversification of T cell signaling pathways following activation of the T-cell antigen receptor (
TCR) signal transduction pathway, which is first catalyzed by TCR binding to
MHC class II. LAT is a 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] In mouse thymocytes, lack of functional LAT or the inability for LAT to be phosphorylated leads to complete lack of T cell development. Moreover, mutation and deletion of LAT hampers overall TCR mediated T cell response.[8]
ZAP-70 phosphorylates tyrosines on LAT, specifically tyrosines 171, 191, and 226 is able to interact with adaptor proteins that have a
SH2 domain, and are members of the
Grb2 protein family, such as Gads.[11][9] Moreover, phosphorylation of LAT tyrosine 132 allows for
PLCγ1-LAT association, which, when combined with concurrent
Gads binding to tyrosines 171 or 191 of LAT, allows for the formation of a LAT-nucleated signaling complex. LAT-interacting Gads attracts the binding of
SLP-76, which recruits additional effector molecules that assist in the stabilization of
PLCγ1 binding to the LAT complex.[11] The resulting LAT signaling complex, which contains the molecules
PLCγ1,
Grb2, Gads,
SLP-76 and the necessary associated ligands thus allow for diversification of the TCR signaling pathway through actin production, the activation of transcription factors, and other messaging signals.[11]
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.[12] 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][13]
Interactions
The Linker for Activation of T cells has been shown to
interact with:
^
abcdePerez-Villar JJ, Whitney GS, Sitnick MT, Dunn RJ, Venkatesan S, O'Day K, et al. (August 2002). "Phosphorylation of the linker for activation of T-cells by Itk promotes recruitment of Vav". Biochemistry. 41 (34): 10732–10740.
doi:
10.1021/bi025554o.
PMID12186560.
Wange RL (December 2000). "LAT, the linker for activation of T cells: a bridge between T cell-specific and general signaling pathways". Science's STKE. 2000 (63): re1.
doi:
10.1126/stke.2000.63.re1.
PMID11752630.
S2CID31968793.
Sommers CL, Samelson LE, Love PE (January 2004). "LAT: a T lymphocyte adapter protein that couples the antigen receptor to downstream signaling pathways". BioEssays. 26 (1): 61–67.
doi:
10.1002/bies.10384.
PMID14696041.
Rivera J (March 2005). "NTAL/LAB and LAT: a balancing act in mast-cell activation and function". Trends in Immunology. 26 (3): 119–122.
doi:
10.1016/j.it.2005.01.001.
PMID15745852.
The LAT protein encoded by the gene of the same name, plays a key role in the diversification of T cell signaling pathways following activation of the T-cell antigen receptor (
TCR) signal transduction pathway, which is first catalyzed by TCR binding to
MHC class II. LAT is a 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] In mouse thymocytes, lack of functional LAT or the inability for LAT to be phosphorylated leads to complete lack of T cell development. Moreover, mutation and deletion of LAT hampers overall TCR mediated T cell response.[8]
ZAP-70 phosphorylates tyrosines on LAT, specifically tyrosines 171, 191, and 226 is able to interact with adaptor proteins that have a
SH2 domain, and are members of the
Grb2 protein family, such as Gads.[11][9] Moreover, phosphorylation of LAT tyrosine 132 allows for
PLCγ1-LAT association, which, when combined with concurrent
Gads binding to tyrosines 171 or 191 of LAT, allows for the formation of a LAT-nucleated signaling complex. LAT-interacting Gads attracts the binding of
SLP-76, which recruits additional effector molecules that assist in the stabilization of
PLCγ1 binding to the LAT complex.[11] The resulting LAT signaling complex, which contains the molecules
PLCγ1,
Grb2, Gads,
SLP-76 and the necessary associated ligands thus allow for diversification of the TCR signaling pathway through actin production, the activation of transcription factors, and other messaging signals.[11]
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.[12] 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][13]
Interactions
The Linker for Activation of T cells has been shown to
interact with:
^
abcdePerez-Villar JJ, Whitney GS, Sitnick MT, Dunn RJ, Venkatesan S, O'Day K, et al. (August 2002). "Phosphorylation of the linker for activation of T-cells by Itk promotes recruitment of Vav". Biochemistry. 41 (34): 10732–10740.
doi:
10.1021/bi025554o.
PMID12186560.
Wange RL (December 2000). "LAT, the linker for activation of T cells: a bridge between T cell-specific and general signaling pathways". Science's STKE. 2000 (63): re1.
doi:
10.1126/stke.2000.63.re1.
PMID11752630.
S2CID31968793.
Sommers CL, Samelson LE, Love PE (January 2004). "LAT: a T lymphocyte adapter protein that couples the antigen receptor to downstream signaling pathways". BioEssays. 26 (1): 61–67.
doi:
10.1002/bies.10384.
PMID14696041.
Rivera J (March 2005). "NTAL/LAB and LAT: a balancing act in mast-cell activation and function". Trends in Immunology. 26 (3): 119–122.
doi:
10.1016/j.it.2005.01.001.
PMID15745852.