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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