Gene interactions and pathways from curated databases and text-mining
J Biol Chem 1996, PMID: 8702662

Phosphorylation of SLP-76 by the ZAP-70 protein-tyrosine kinase is required for T-cell receptor function.

Bubeck Wardenburg, J; Fu, C; Jackman, J K; Flotow, H; Wilkinson, S E; Williams, D H; Johnson, R; Kong, G; Chan, A C; Findell, P R

Two families of tyrosine kinases, the Src and Syk families, are required for T-cell receptor activation. While the Src kinases are responsible for phosphorylation of receptor-encoded signaling motifs and for up-regulation of ZAP-70 activity, the downstream substrates of ZAP-70 are unknown. Evidence is presented herein that the Src homology 2 (SH2) domain-containing leukocyte protein of 76 kDa (SLP-76) is a substrate of ZAP-70. Phosphorylation of SLP-76 is diminished in T cells that express a catalytically inactive ZAP-70. Moreover, SLP-76 is preferentially phosphorylated by ZAP-70 in vitro and in heterologous cellular systems. In T cells, overexpression of wild-type SLP-76 results in a hyperactive receptor, while expression of a SLP-76 molecule that is unable to be tyrosine-phosphorylated attenuates receptor function. In addition, the SH2 domain of SLP-76 is required for T-cell receptor function, although its role is independent of the ability of SLP-76 to undergo tyrosine phosphorylation. As SLP-76 interacts with both Grb2 and phospholipase C-gamma1, these data indicate that phosphorylation of SLP-76 by ZAP-70 provides an important functional link between the T-cell receptor and activation of ras and calcium pathways.

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Text Mining Data

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Manually curated Databases

  • IRef Hprd Interaction: ZAP70 — LCP2 (in vitro)
  • IRef Hprd Interaction: ZAP70 — LCP2 (in vivo)
  • IRef Hprd Interaction: LCK — LCP2 (in vitro)
  • IRef Hprd Interaction: LCK — LCP2 (in vivo)
  • IRef Hprd Interaction: TXK — LCP2 (in vivo)
  • IRef Hprd Interaction: TXK — LCP2 (in vitro)
  • Reactome Reaction: GRAP2 → IGLC3 (reaction)
  • Reactome Reaction: IGHE → SOS1 (reaction)
  • Reactome Reaction: IGKV1-5 → SOS1 (reaction)
  • Reactome Reaction: GRB2 → HLA-E (reaction)
  • Reactome Reaction: KLRC2 → LAT (reaction)
  • Reactome Reaction: IGKV4-1 → PLCG1 (reaction)
  • Reactome Reaction: FYN → PLCG2 (reaction)
  • Reactome Reaction: B2M → PLCG2 (reaction)
  • Reactome Reaction: KLRK1 → SOS1 (reaction)
  • Reactome Reaction: LCP2 → SHC1 (indirect_complex)
  • Reactome Reaction: GRB2 → IGLC2 (reaction)
  • Reactome Reaction: LYN → SOS1 (reaction)
  • Reactome Reaction: GRAP2 → KLRC2 (reaction)
  • Reactome Reaction: GRB2 → IGLC6 (reaction)
  • Reactome Reaction: LCP2 → KLRC2 (reaction)
  • Reactome Reaction: LCP2 → PLCG2 (indirect_complex)
  • Reactome Reaction: IGKV4-1 → PLCG2 (reaction)
  • Reactome Reaction: IGKV4-1 → SOS1 (reaction)
  • Reactome Reaction: SHC1 → IGLC1 (reaction)
  • Reactome Reaction: IGKC → PLCG2 (reaction)
  • Reactome Reaction: B2M → LAT (reaction)
  • Reactome Reaction: PLCG1 → IGLC7 (reaction)
  • Reactome Reaction: LYN → PLCG2 (reaction)
  • Reactome Reaction: B2M → SHC1 (reaction)
  • Reactome Reaction: LYN → SHC1 (reaction)
  • Reactome Reaction: LCK → LCP2 (reaction)
  • Reactome Reaction: GRB2 → KLRK1 (reaction)
  • Reactome Reaction: PLCG2 → IGLC3 (reaction)
  • Reactome Reaction: SHC1 → IGLC7 (reaction)
  • Reactome Reaction: SYK → PLCG1 (reaction)
  • Reactome Reaction: LCP2 → LAT (indirect_complex)
  • Reactome Reaction: LCK → PLCG2 (reaction)
  • Reactome Reaction: IGHE → GRAP2 (reaction)
  • Reactome Reaction: LCK → PLCG1 (reaction)
  • Reactome Reaction: FYN → LAT (reaction)
  • Reactome Reaction: IGHE → SHC1 (reaction)
  • Reactome Reaction: IGKC → LCP2 (reaction)
  • Reactome Reaction: LAT → TREM2 (reaction)
  • Reactome Reaction: LAT → IGLC6 (reaction)
  • Reactome Reaction: GRAP2 → IGLC2 (reaction)
  • Reactome Reaction: SYK → LAT (reaction)
  • Reactome Reaction: PLCG2 → IGLC1 (reaction)
  • Reactome Reaction: PLCG1 → TREM2 (reaction)
  • Reactome Reaction: GRB2 → KLRC2 (reaction)
  • Reactome Reaction: LCP2 → SOS1 (indirect_complex)
  • Reactome Reaction: GRB2 → KLRD1 (reaction)
  • Reactome Reaction: B2M → SOS1 (reaction)
  • Reactome Reaction: IGHE → GRB2 (reaction)
  • Reactome Reaction: KLRK1 → PLCG2 (reaction)
  • Reactome Reaction: IGHE → PLCG2 (reaction)
  • Reactome Reaction: PLCG2 → KLRD1 (reaction)
  • Reactome Reaction: FYN → SOS1 (reaction)
  • Reactome Reaction: B2M → GRB2 (reaction)
  • Reactome Reaction: IGKV1-5 → LCP2 (reaction)
  • Reactome Reaction: SOS1 → IGLC7 (reaction)
  • Reactome Reaction: HLA-E → PLCG2 (reaction)
  • Reactome Reaction: PLCG2 → SHC1 (indirect_complex)
  • Reactome Reaction: GRAP2 → PLCG2 (indirect_complex)
  • Reactome Reaction: LAT → IGLC1 (reaction)
  • Reactome Reaction: PLCG2 → IGLC6 (reaction)
  • Reactome Reaction: GRAP2 → IGKV4-1 (reaction)
  • Reactome Reaction: IGKV1-5 → PLCG2 (reaction)
  • Reactome Reaction: HLA-E → LAT (reaction)
  • Reactome Reaction: TYROBP → SHC1 (reaction)
  • Reactome Reaction: FYN → SHC1 (reaction)
  • Reactome Reaction: SHC1 → IGLC3 (reaction)
  • Reactome Reaction: IGHE → LAT (reaction)
  • Reactome Reaction: HLA-E → LCP2 (reaction)
  • Reactome Reaction: LAT → KLRD1 (reaction)
  • Reactome Reaction: LCK → SOS1 (reaction)
  • Reactome Reaction: PLCG2 → IGLC2 (reaction)
  • Reactome Reaction: FYN → GRB2 (reaction)
  • Reactome Reaction: HLA-E → PLCG1 (reaction)
  • Reactome Reaction: LCP2 → LYN (reaction)
  • Reactome Reaction: SOS1 → IGLC3 (reaction)
  • Reactome Reaction: GRB2 → IGKV1-5 (reaction)
  • Reactome Reaction: GRAP2 → LCK (reaction)
  • Reactome Reaction: PLCG1 → SOS1 (indirect_complex)
  • Reactome Reaction: IGKV4-1 → LAT (reaction)
  • Reactome Reaction: GRAP2 → LYN (reaction)
  • Reactome Reaction: IGKV4-1 → LCP2 (reaction)
  • Reactome Reaction: B2M → LCP2 (reaction)
  • Reactome Reaction: SOS1 → IGLC2 (reaction)
  • Reactome Reaction: GRAP2 → IGLC7 (reaction)
  • Reactome Reaction: SYK → SOS1 (reaction)
  • Reactome Reaction: KLRC2 → SOS1 (reaction)
  • Reactome Reaction: LAT → IGLC2 (reaction)
  • Reactome Reaction: GRAP2 → TREM2 (reaction)
  • Reactome Reaction: IGKV1-5 → PLCG1 (reaction)
  • Reactome Reaction: LCP2 → KLRD1 (reaction)
  • Reactome Reaction: PLCG1 → LAT (indirect_complex)
  • Reactome Reaction: GRAP2 → IGKV1-5 (reaction)
  • Reactome Reaction: GRB2 → IGKC (reaction)
  • Reactome Reaction: IGKV1-5 → LAT (reaction)
  • Reactome Reaction: SHC1 → IGLC2 (reaction)
  • Reactome Reaction: SOS1 → KLRD1 (reaction)
  • Reactome Reaction: PLCG2 → SOS1 (indirect_complex)
  • Reactome Reaction: SHC1 → IGLC6 (reaction)
  • Reactome Reaction: FYN → GRAP2 (reaction)
  • Reactome Reaction: GRB2 → IGLC7 (reaction)
  • Reactome Reaction: LCK → LAT (reaction)
  • Reactome Reaction: B2M → PLCG1 (reaction)
  • Reactome Reaction: GRAP2 → IGKC (reaction)
  • Reactome Reaction: FYN → PLCG1 (reaction)
  • Reactome Reaction: B2M → GRAP2 (reaction)
  • Reactome Reaction: TREM2 → SHC1 (reaction)
  • Reactome Reaction: LCP2 → PLCG1 (indirect_complex)
  • Reactome Reaction: LCP2 → IGLC7 (reaction)
  • Reactome Reaction: SYK → PLCG2 (reaction)
  • Reactome Reaction: SOS1 → TYROBP (reaction)
  • Reactome Reaction: PLCG1 → IGLC6 (reaction)
  • Reactome Reaction: IGKC → PLCG1 (reaction)
  • Reactome Reaction: LCP2 → TYROBP (reaction)
  • Reactome Reaction: GRB2 → SYK (reaction)
  • Reactome Reaction: GRAP2 → KLRD1 (reaction)
  • Reactome Reaction: LYN → PLCG1 (reaction)
  • Reactome Reaction: SYK → SHC1 (reaction)
  • Reactome Reaction: GRB2 → IGLC1 (reaction)
  • Reactome Reaction: GRB2 → LCK (reaction)
  • Reactome Reaction: GRAP2 → LAT (indirect_complex)
  • Reactome Reaction: LCP2 → IGLC1 (reaction)
  • Reactome Reaction: GRB2 → IGKV4-1 (reaction)
  • Reactome Reaction: LCP2 → TREM2 (reaction)
  • Reactome Reaction: SHC1 → KLRD1 (reaction)
  • Reactome Reaction: SYK → LCP2 (reaction)
  • Reactome Reaction: HLA-E → SOS1 (reaction)
  • Reactome Reaction: IGKV4-1 → SHC1 (reaction)
  • Reactome Reaction: HLA-E → SHC1 (reaction)
  • Reactome Reaction: GRB2 → TYROBP (reaction)
  • Reactome Reaction: GRAP2 → IGLC1 (reaction)
  • Reactome Reaction: TYROBP → LAT (reaction)
  • Reactome Reaction: KLRC2 → PLCG1 (reaction)
  • Reactome Reaction: LAT → IGLC3 (reaction)
  • Reactome Reaction: IGKC → SHC1 (reaction)
  • Reactome Reaction: KLRK1 → PLCG1 (reaction)
  • Reactome Reaction: KLRK1 → LAT (reaction)
  • Reactome Reaction: GRAP2 → SYK (reaction)
  • Reactome Reaction: IGKC → LAT (reaction)
  • Reactome Reaction: LYN → LAT (reaction)
  • Reactome Reaction: GRAP2 → HLA-E (reaction)
  • Reactome Reaction: GRAP2 → KLRK1 (reaction)
  • Reactome Reaction: IGKC → SOS1 (reaction)
  • Reactome Reaction: FYN → LCP2 (reaction)
  • Reactome Reaction: KLRC2 → PLCG2 (reaction)
  • Reactome Reaction: GRB2 → GRAP2 (indirect_complex)
  • Reactome Reaction: PLCG1 → IGLC2 (reaction)
  • Reactome Reaction: LAT → IGLC7 (reaction)
  • Reactome Reaction: GRB2 → LCP2 (indirect_complex)
  • Reactome Reaction: LCP2 → IGLC3 (reaction)
  • Reactome Reaction: GRB2 → IGLC3 (reaction)
  • Reactome Reaction: PLCG1 → TYROBP (reaction)
  • Reactome Reaction: GRAP2 → PLCG1 (indirect_complex)
  • Reactome Reaction: PLCG1 → IGLC3 (reaction)
  • Reactome Reaction: PLCG1 → IGLC1 (reaction)
  • Reactome Reaction: IGHE → LCP2 (reaction)
  • Reactome Reaction: LCP2 → IGLC6 (reaction)
  • Reactome Reaction: SOS1 → TREM2 (reaction)
  • Reactome Reaction: PLCG2 → LAT (indirect_complex)
  • Reactome Reaction: PLCG1 → KLRD1 (reaction)
  • Reactome Reaction: PLCG2 → IGLC7 (reaction)
  • Reactome Reaction: LCK → SHC1 (reaction)
  • Reactome Reaction: IGKV1-5 → SHC1 (reaction)
  • Reactome Reaction: LCP2 → IGLC2 (reaction)
  • Reactome Reaction: KLRK1 → SHC1 (reaction)
  • Reactome Reaction: PLCG2 → TREM2 (reaction)
  • Reactome Reaction: LCP2 → KLRK1 (reaction)
  • Reactome Reaction: KLRC2 → SHC1 (reaction)
  • Reactome Reaction: GRB2 → TREM2 (reaction)
  • Reactome Reaction: GRAP2 → SOS1 (indirect_complex)
  • Reactome Reaction: SOS1 → IGLC1 (reaction)
  • Reactome Reaction: GRAP2 → SHC1 (indirect_complex)
  • Reactome Reaction: PLCG1 → SHC1 (indirect_complex)
  • Reactome Reaction: IGHE → PLCG1 (reaction)
  • Reactome Reaction: PLCG2 → TYROBP (reaction)
  • Reactome Reaction: GRAP2 → IGLC6 (reaction)
  • Reactome Reaction: GRB2 → LYN (reaction)
  • Reactome Reaction: GRAP2 → TYROBP (reaction)
  • Reactome Reaction: GRB2 → PLCG1 (indirect_complex)
  • Reactome Reaction: SOS1 → IGLC6 (reaction)
  • Reactome Reaction: GRB2 → PLCG2 (indirect_complex)
In total, 182 gene pairs are associated to this article in curated databases