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LAT — ZAP70
Pathways - manually collected, often from reviews:
-
KEGG Natural killer cell mediated cytotoxicity:
ZAP70
→
LAT
(protein-protein, activation)
-
KEGG Natural killer cell mediated cytotoxicity:
ZAP70
→
LAT
(protein-protein, activation)
-
KEGG T cell receptor signaling pathway:
ZAP70
→
LAT
(protein-protein, phosphorylation)
-
NCI Pathway Database TCR signaling in naïve CD4+ T cells:
LAT/GRAP2/SLP76 complex (LAT-GRAP2-LCP2)
→
TCR/CD3/MHC II/CD4/LCK/ZAP-70 complex (CD247-CD3E-CD3G-CD3D-HLA-DRA-HLA-DRB1-CD4-LCK-ZAP70)
(modification, collaborate)
Liu et al., J Immunol 2000
Evidence: mutant phenotype, physical interaction, other species
-
NCI Pathway Database Class I PI3K signaling events:
Src family/SYK family/BLNK-LAT complex (FGR_LYN_LCK_YES1_BLK_HCK_SRC_FYN-ZAP70_SYK-BLNK_LAT)
→
Src family/SYK family/BLNK-LAT/BTK-ITK complex (FGR_LYN_LCK_YES1_BLK_HCK_SRC_FYN-ZAP70_SYK-BLNK_LAT-ITK_BTK)
(modification, collaborate)
Shan et al., J Biol Chem 1999, Baba et al., Proc Natl Acad Sci U S A 2001, Rawlings et al., Science 1996, August et al., Proc Natl Acad Sci U S A 1997
Evidence: mutant phenotype, physical interaction, other species
-
NCI Pathway Database Class I PI3K signaling events:
Src family/SYK family/BLNK-LAT complex (FGR_LYN_LCK_YES1_BLK_HCK_SRC_FYN-ZAP70_SYK-BLNK_LAT)
→
BTK-ITK (ITK/BTK)
(modification, collaborate)
Shan et al., J Biol Chem 1999, Baba et al., Proc Natl Acad Sci U S A 2001, Rawlings et al., Science 1996, August et al., Proc Natl Acad Sci U S A 1997
Evidence: mutant phenotype, physical interaction, other species
-
NCI Pathway Database Class I PI3K signaling events:
Src family/SYK family/BLNK-LAT/BTK-ITK complex (FGR_LYN_LCK_YES1_BLK_HCK_SRC_FYN-ZAP70_SYK-BLNK_LAT-ITK_BTK)
→
BTK-ITK (ITK/BTK)
(modification, collaborate)
Shan et al., J Biol Chem 1999, Baba et al., Proc Natl Acad Sci U S A 2001, Rawlings et al., Science 1996, August et al., Proc Natl Acad Sci U S A 1997
Evidence: mutant phenotype, physical interaction, other species
-
NCI Pathway Database Class I PI3K signaling events:
None
→
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma complex (FGR_LYN_LCK_YES1_BLK_HCK_SRC_FYN-ZAP70_SYK-BLNK_LAT-ITK_BTK-PLCG1_PLCG2)
(modification, collaborate)
Rodriguez et al., Biochem J 2003
Evidence: mutant phenotype, other species
-
NCI Pathway Database Class I PI3K signaling events:
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma complex (FGR_LYN_LCK_YES1_BLK_HCK_SRC_FYN-ZAP70_SYK-BLNK_LAT-ITK_BTK-PLCG1_PLCG2)
(modification, activates)
Rodriguez et al., Biochem J 2003
Evidence: mutant phenotype, other species
-
NCI Pathway Database Class I PI3K signaling events:
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma complex (FGR_LYN_LCK_YES1_BLK_HCK_SRC_FYN-ZAP70_SYK-BLNK_LAT-ITK_BTK-PLCG1_PLCG2)
→
None
(modification, activates)
Rodriguez et al., Biochem J 2003
Evidence: mutant phenotype, other species
-
NCI Pathway Database Class I PI3K signaling events:
PLC-gamma family (PLCG1/PLCG2)
→
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma complex (FGR_LYN_LCK_YES1_BLK_HCK_SRC_FYN-ZAP70_SYK-BLNK_LAT-ITK_BTK-PLCG1_PLCG2)
(modification, collaborate)
Perez-Villar et al., J Immunol 1999, Rodriguez et al., Biochem J 2003, Serrano et al., J Immunol 2005
Evidence: mutant phenotype, physical interaction, other species
-
NCI Pathway Database Class I PI3K signaling events:
PLC-gamma family (PLCG1/PLCG2)
→
Src family/SYK family/BLNK-LAT/BTK-ITK complex (FGR_LYN_LCK_YES1_BLK_HCK_SRC_FYN-ZAP70_SYK-BLNK_LAT-ITK_BTK)
(modification, collaborate)
Perez-Villar et al., J Immunol 1999, Rodriguez et al., Biochem J 2003, Serrano et al., J Immunol 2005
Evidence: mutant phenotype, physical interaction, other species
-
NCI Pathway Database Class I PI3K signaling events:
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma complex (FGR_LYN_LCK_YES1_BLK_HCK_SRC_FYN-ZAP70_SYK-BLNK_LAT-ITK_BTK-PLCG1_PLCG2)
→
Src family/SYK family/BLNK-LAT/BTK-ITK complex (FGR_LYN_LCK_YES1_BLK_HCK_SRC_FYN-ZAP70_SYK-BLNK_LAT-ITK_BTK)
(modification, collaborate)
Perez-Villar et al., J Immunol 1999, Rodriguez et al., Biochem J 2003, Serrano et al., J Immunol 2005
Evidence: mutant phenotype, physical interaction, other species
-
NCI Pathway Database TCR signaling in naïve CD8+ T cells:
LAT/GRAP2/SLP76/VAV1/PI3K Class IA complex (LAT-GRAP2-LCP2-VAV1)
→
TCR/CD3/MHC I/CD8/LCK/ZAP-70 complex (CD247-CD3E-CD3G-CD3D-HLA-A-B2M-CD8A-CD8B-LCK-ZAP70)
(modification, activates)
Villalba et al., J Cell Biol 2002, Reynolds et al., J Biol Chem 2004
Evidence: mutant phenotype, other species
-
Reactome Reaction:
LAT
→
ZAP70
(reaction)
Zhang et al., J Biol Chem 2000, Kim et al., Exp Mol Med 2000, Wange et al., Science's STKE : signal transduction knowledge environment 2000, Rudd et al., Am J Transplant 2003, Qi et al., Science's STKE : signal transduction knowledge environment 2007
-
WikiPathways T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection:
ZAP70
→
LAT
(activation)
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
-
IRef Biogrid Interaction:
LAT
—
ZAP70
(colocalization, imaging technique)
Houtman et al., Nature structural & molecular biology 2006*
-
IRef Biogrid Interaction:
LAT
—
ZAP70
(physical association, affinity chromatography technology)
Xie et al., J Immunol 2013*
-
IRef Biogrid Interaction:
LAT
—
ZAP70
(direct interaction, enzymatic study)
Paz et al., Biochem J 2001
-
IRef Biogrid Interaction:
LAT
—
ZAP70
(direct interaction, enzymatic study)
Perez-Villar et al., Biochemistry 2002
-
IRef Hprd Interaction:
LAT
—
ZAP70
(in vivo)
Paz et al., Biochem J 2001
-
IRef Hprd Interaction:
LAT
—
ZAP70
(in vitro)
Paz et al., Biochem J 2001
-
IRef Intact Interaction:
ZAP70
—
LAT
(colocalization, imaging technique)
Houtman et al., Nature structural & molecular biology 2006*
Text-mined interactions from Literome
Thien et al., J Immunol 1999
:
These findings provide evidence that c-Cbl is involved in the negative
regulation of the phosphorylation of
LAT and SLP-76 by
ZAP-70
Graham et al., Oncogene 2003
:
70Z/3 Cbl induced PLC gamma 1 phosphorylation required
Zap-70 , as for the TCR, and the tyrosine kinase binding domain of 70Z/3 Cbl, which binds Zap-70, but did not
require PLC gamma 1 binding to
Lat , a crucial interaction in TCR induced PLC gamma 1 phosphorylation
Kim et al., Biochem Biophys Res Commun 2009
:
Hph-1-ZAP-70-Y319F inhibited the phosphorylation of ZAP-70-Tyr319,
LAT-Tyr191 , and p44/42 MAPK induced by TcR stimulation, NFAT- and AP-1 mediated gene transcription, and the induction of CD69 expression and IL-2 secretion
Dong et al., PloS one 2010
:
Strikingly, upon LAT knockdown in Hut-78 cells, we found that
LAT promoted TCR induced phosphorylation of Lck and Fyn activatory tyrosines, TCR? chain phosphorylation and
Zap-70 activation