Gene interactions and pathways from curated databases and text-mining
J Biol Chem 2005, PMID: 15536084

Molecular basis for a direct interaction between the Syk protein-tyrosine kinase and phosphoinositide 3-kinase.

Moon, Kyung D; Post, Carol B; Durden, Donald L; Zhou, Qing; De, Pradip; Harrison, Marietta L; Geahlen, Robert L

After engagement of the B cell receptor for antigen, the Syk protein-tyrosine kinase becomes phosphorylated on multiple tyrosines, some of which serve as docking sites for downstream effectors with SH2 or other phosphotyrosine binding domains. The most frequently identified binding partner for catalytically active Syk identified in a yeast two-hybrid screen was the p85 regulatory subunit of phosphoinositide 3-kinase. The C-terminal SH2 domain of p85 was sufficient for mediating an interaction with tyrosine-phosphorylated Syk. Interestingly, this domain interacted with Syk at phosphotyrosine 317, a site phosphorylated in trans by the Src family kinase, Lyn, and identified previously as a binding site for c-Cbl. This site interacted preferentially with the p85 C-terminal SH2 domain compared with the c-Cbl tyrosine kinase binding domain. Molecular modeling studies showed a good fit between the p85 SH2 domain and a peptide containing phosphotyrosine 317. Tyr-317 was found to be essential for Syk to support phagocytosis mediated by FcgammaRIIA receptors expressed in a heterologous system. These studies establish a new type of p85 binding site that can exist on proteins that serve as substrates for Src family kinases and provide a molecular explanation for observations on direct interactions between Syk and phosphoinositide 3-kinase.

Document information provided by NCBI PubMed

Text Mining Data

Dashed line = No text mining data

Manually curated Databases

  • IRef Biogrid Interaction: SYK — CBL (direct interaction, pull down)
  • IRef Biogrid Interaction: PIK3R1 — ZAP70 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: RPS10 — SYK (direct interaction, two hybrid)
  • IRef Biogrid Interaction: RPS10 — TP53 (direct interaction, two hybrid)
  • IRef Biogrid Interaction: PIK3R2 — SYK (direct interaction, two hybrid)
  • IRef Biogrid Interaction: SYK — PIK3R1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: SYK — PIK3R1 (direct interaction, pull down)
  • IRef Biogrid Interaction: SYK — PIK3R1 (direct interaction, two hybrid)
  • IRef Biogrid Interaction: LCK — SYK (direct interaction, two hybrid)
  • IRef Biogrid Interaction: SYK — FGR (direct interaction, two hybrid)
  • IRef Hprd Interaction: PIK3R2 — SYK (two hybrid)
  • IRef Hprd Interaction: SYK — PIK3R1 (two hybrid)
  • IRef Intact Interaction: PIK3R2 — SYK (physical association, two hybrid)
  • IRef Intact Interaction: SYK — PIK3R1 (physical association, pull down)
  • IRef Intact Interaction: SYK — PIK3R1 (physical association, two hybrid)
  • IRef Intact Interaction: SYK — PIK3R1 (physical association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: LCK — SYK (physical association, two hybrid)
  • IRef Intact Interaction: SYK — FGR (physical association, two hybrid)
  • Reactome Reaction: SYK → LCK (indirect_complex)
  • Reactome Reaction: PIK3R2 → IGLC7 (indirect_complex)
  • Reactome Reaction: CD247 → PIK3R1 (indirect_complex)
  • Reactome Reaction: HLA-E → PIK3R2 (reaction)
  • Reactome Reaction: HLA-E → PIK3CA (reaction)
  • Reactome Reaction: IGKV4-1 → PIK3R1 (reaction)
  • Reactome Reaction: HLA-E → PIK3R1 (reaction)
  • Reactome Reaction: SYK → PIK3CA (indirect_complex)
  • Reactome Reaction: PIK3CA → IGLC7 (reaction)
  • Reactome Reaction: FCGR1A → PIK3R2 (indirect_complex)
  • Reactome Reaction: B2M → SYK (indirect_complex)
  • Reactome Reaction: IGHG2 → PIK3R1 (reaction)
  • Reactome Reaction: SYK → PIK3CA (reaction)
  • Reactome Reaction: IGHG2 → PIK3CA (indirect_complex)
  • Reactome Reaction: KLRC2 → PIK3R2 (reaction)
  • Reactome Reaction: IGHG4 → PIK3CB (indirect_complex)
  • Reactome Reaction: IGHG4 → PIK3CA (reaction)
  • Reactome Reaction: FYN → PIK3R2 (indirect_complex)
  • Reactome Reaction: FCGR2A → PIK3R2 (reaction)
  • Reactome Reaction: FYN → SYK (indirect_complex)
  • Reactome Reaction: IGHG1 → PIK3CA (reaction)
  • Reactome Reaction: IGHG2 → PIK3R2 (reaction)
  • Reactome Reaction: PIK3R1 → IGLC1 (indirect_complex)
  • Reactome Reaction: IGKV1-5 → PIK3CB (indirect_complex)
  • Reactome Reaction: KLRK1 → PIK3R1 (indirect_complex)
  • Reactome Reaction: IGKV4-1 → PIK3CB (indirect_complex)
  • Reactome Reaction: FCGR2A → PIK3R1 (reaction)
  • Reactome Reaction: FYN → PIK3CA (reaction)
  • Reactome Reaction: IGHG1 → PIK3R1 (indirect_complex)
  • Reactome Reaction: SYK → PIK3R1 (indirect_complex)
  • Reactome Reaction: KLRK1 → PIK3CB (indirect_complex)
  • Reactome Reaction: PIK3CB → IGLC2 (indirect_complex)
  • Reactome Reaction: KLRK1 → PIK3R2 (reaction)
  • Reactome Reaction: CD247 → PIK3CB (indirect_complex)
  • Reactome Reaction: CD247 → PIK3CB (reaction)
  • Reactome Reaction: HLA-E → PIK3CA (indirect_complex)
  • Reactome Reaction: SYK → TYROBP (indirect_complex)
  • Reactome Reaction: B2M → PIK3CA (reaction)
  • Reactome Reaction: PIK3R1 → IGLC7 (indirect_complex)
  • Reactome Reaction: PIK3R2 → TYROBP (indirect_complex)
  • Reactome Reaction: FCGR1A → PIK3CA (reaction)
  • Reactome Reaction: IGHG2 → PIK3R1 (indirect_complex)
  • Reactome Reaction: IGHG3 → PIK3CB (indirect_complex)
  • Reactome Reaction: PIK3R1 → TREM2 (reaction)
  • Reactome Reaction: PIK3R1 → IGLC1 (reaction)
  • Reactome Reaction: PIK3R1 → TYROBP (indirect_complex)
  • Reactome Reaction: CD3G → PIK3CB (indirect_complex)
  • Reactome Reaction: PIK3CA → IGLC2 (reaction)
  • Reactome Reaction: IGKC → PIK3CB (indirect_complex)
  • Reactome Reaction: IGKC → PIK3CA (indirect_complex)
  • Reactome Reaction: PIK3CB → IGLC1 (indirect_complex)
  • Reactome Reaction: PIK3R2 → IGLC3 (reaction)
  • Reactome Reaction: IGKV1-5 → PIK3R1 (indirect_complex)
  • Reactome Reaction: LCK → PIK3R1 (reaction)
  • Reactome Reaction: IGKC → PIK3CB (reaction)
  • Reactome Reaction: PIK3R1 → TREM2 (indirect_complex)
  • Reactome Reaction: PIK3R1 → IGLC7 (reaction)
  • Reactome Reaction: PIK3CA → TYROBP (reaction)
  • Reactome Reaction: IGHG2 → PIK3CB (indirect_complex)
  • Reactome Reaction: IGHG2 → PIK3CB (reaction)
  • Reactome Reaction: PIK3R2 → IGLC1 (reaction)
  • Reactome Reaction: PIK3CB → TYROBP (reaction)
  • Reactome Reaction: PIK3CB → IGLC7 (reaction)
  • Reactome Reaction: PIK3CA → IGLC2 (indirect_complex)
  • Reactome Reaction: KLRC2 → PIK3CB (indirect_complex)
  • Reactome Reaction: FCGR3A → PIK3R1 (indirect_complex)
  • Reactome Reaction: SYK → PIK3R1 (reaction)
  • Reactome Reaction: PIK3R2 → IGLC2 (indirect_complex)
  • Reactome Reaction: PIK3R2 → TREM2 (reaction)
  • Reactome Reaction: PIK3CB → TYROBP (indirect_complex)
  • Reactome Reaction: IGHG3 → PIK3CA (indirect_complex)
  • Reactome Reaction: IGHG3 → PIK3CA (reaction)
  • Reactome Reaction: B2M → PIK3CA (indirect_complex)
  • Reactome Reaction: PIK3R2 → IGLC3 (indirect_complex)
  • Reactome Reaction: CD3G → PIK3CA (indirect_complex)
  • Reactome Reaction: KLRK1 → PIK3R1 (reaction)
  • Reactome Reaction: KLRC2 → PIK3CA (indirect_complex)
  • Reactome Reaction: IGHG3 → PIK3R1 (indirect_complex)
  • Reactome Reaction: IGHG3 → PIK3R2 (indirect_complex)
  • Reactome Reaction: KLRK1 → PIK3R2 (indirect_complex)
  • Reactome Reaction: PIK3CA → IGLC7 (indirect_complex)
  • Reactome Reaction: KLRC2 → PIK3CA (reaction)
  • Reactome Reaction: IGKC → PIK3CA (reaction)
  • Reactome Reaction: IGHG2 → PIK3R2 (indirect_complex)
  • Reactome Reaction: PIK3R2 → KLRD1 (reaction)
  • Reactome Reaction: CD3G → PIK3CB (reaction)
  • Reactome Reaction: FYN → PIK3CB (indirect_complex)
  • Reactome Reaction: PIK3CA → IGLC6 (reaction)
  • Reactome Reaction: CD247 → PIK3R1 (reaction)
  • Reactome Reaction: CD247 → PIK3CA (reaction)
  • Reactome Reaction: IGKC → PIK3R2 (reaction)
  • Reactome Reaction: PIK3CB → KLRD1 (reaction)
  • Reactome Reaction: PIK3R2 → TYROBP (reaction)
  • Reactome Reaction: IGHG2 → PIK3CA (reaction)
  • Reactome Reaction: KLRC2 → PIK3R1 (indirect_complex)
  • Reactome Reaction: HLA-E → PIK3CB (reaction)
  • Reactome Reaction: CD247 → PIK3R2 (reaction)
  • Reactome Reaction: SYK → KLRD1 (indirect_complex)
  • Reactome Reaction: FCGR1A → PIK3R1 (reaction)
  • Reactome Reaction: PIK3CA → KLRD1 (reaction)
  • Reactome Reaction: FCGR3A → PIK3R1 (reaction)
  • Reactome Reaction: FCGR2A → PIK3CB (indirect_complex)
  • Reactome Reaction: PIK3CB → KLRD1 (indirect_complex)
  • Reactome Reaction: IGHG1 → PIK3R2 (reaction)
  • Reactome Reaction: FYN → PIK3R1 (reaction)
  • Reactome Reaction: FCGR2A → PIK3R1 (indirect_complex)
  • Reactome Reaction: IGKV4-1 → PIK3R1 (indirect_complex)
  • Reactome Reaction: FCGR3A → PIK3CA (reaction)
  • Reactome Reaction: FCGR2A → PIK3R2 (indirect_complex)
  • Reactome Reaction: FYN → PIK3R1 (indirect_complex)
  • Reactome Reaction: FCGR1A → PIK3R1 (indirect_complex)
  • Reactome Reaction: PIK3CA → IGLC1 (reaction)
  • Reactome Reaction: B2M → PIK3CB (indirect_complex)
  • Reactome Reaction: SYK → TREM2 (indirect_complex)
  • Reactome Reaction: CD247 → PIK3R2 (indirect_complex)
  • Reactome Reaction: IGHG1 → PIK3R2 (indirect_complex)
  • Reactome Reaction: IGHG4 → PIK3R2 (indirect_complex)
  • Reactome Reaction: FCGR3A → PIK3CA (indirect_complex)
  • Reactome Reaction: LCK → PIK3CA (reaction)
  • Reactome Reaction: IGHG4 → PIK3R1 (indirect_complex)
  • Reactome Reaction: IGHG3 → PIK3CB (reaction)
  • Reactome Reaction: CD3G → PIK3CA (reaction)
  • Reactome Reaction: CD3G → PIK3R1 (reaction)
  • Reactome Reaction: PIK3CA → IGLC6 (indirect_complex)
  • Reactome Reaction: LCK → PIK3CB (indirect_complex)
  • Reactome Reaction: IGHG4 → PIK3CB (reaction)
  • Reactome Reaction: IGHG1 → PIK3CB (reaction)
  • Reactome Reaction: IGHG1 → PIK3CA (indirect_complex)
  • Reactome Reaction: IGKV4-1 → PIK3R2 (indirect_complex)
  • Reactome Reaction: LCK → PIK3R2 (reaction)
  • Reactome Reaction: PIK3CA → IGLC3 (indirect_complex)
  • Reactome Reaction: FCGR1A → PIK3R2 (reaction)
  • Reactome Reaction: SYK → PIK3R2 (reaction)
  • Reactome Reaction: PIK3CB → TREM2 (indirect_complex)
  • Reactome Reaction: PIK3R1 → KLRD1 (indirect_complex)
  • Reactome Reaction: FCGR1A → PIK3CB (indirect_complex)
  • Reactome Reaction: IGKC → PIK3R1 (reaction)
  • Reactome Reaction: PIK3CB → IGLC6 (indirect_complex)
  • Reactome Reaction: IGKV1-5 → PIK3R2 (reaction)
  • Reactome Reaction: SYK → PIK3CB (reaction)
  • Reactome Reaction: IGKV1-5 → PIK3R2 (indirect_complex)
  • Reactome Reaction: PIK3CB → IGLC6 (reaction)
  • Reactome Reaction: PIK3R1 → IGLC6 (reaction)
  • Reactome Reaction: CD3G → PIK3R2 (indirect_complex)
  • Reactome Reaction: FCGR3A → PIK3R2 (reaction)
  • Reactome Reaction: IGKC → PIK3R2 (indirect_complex)
  • Reactome Reaction: IGKC → PIK3R1 (indirect_complex)
  • Reactome Reaction: FCGR2A → PIK3CA (indirect_complex)
  • Reactome Reaction: PIK3R2 → IGLC2 (reaction)
  • Reactome Reaction: IGKV1-5 → PIK3CA (indirect_complex)
  • Reactome Reaction: PIK3CB → IGLC3 (reaction)
  • Reactome Reaction: B2M → PIK3R1 (indirect_complex)
  • Reactome Reaction: B2M → PIK3CB (reaction)
  • Reactome Reaction: SYK → KLRC2 (indirect_complex)
  • Reactome Reaction: IGKV1-5 → PIK3CA (reaction)
  • Reactome Reaction: IGHG4 → PIK3R1 (reaction)
  • Reactome Reaction: PIK3CA → IGLC3 (reaction)
  • Reactome Reaction: KLRK1 → PIK3CA (reaction)
  • Reactome Reaction: PIK3CA → TREM2 (indirect_complex)
  • Reactome Reaction: FCGR1A → PIK3CB (reaction)
  • Reactome Reaction: PIK3CA → TREM2 (reaction)
  • Reactome Reaction: IGKV4-1 → PIK3CA (reaction)
  • Reactome Reaction: FYN → PIK3CA (indirect_complex)
  • Reactome Reaction: SYK → KLRK1 (indirect_complex)
  • Reactome Reaction: PIK3CA → TYROBP (indirect_complex)
  • Reactome Reaction: SYK → PIK3R2 (indirect_complex)
  • Reactome Reaction: IGHG1 → PIK3R1 (reaction)
  • Reactome Reaction: PIK3R1 → IGLC6 (indirect_complex)
  • Reactome Reaction: IGKV4-1 → PIK3R2 (reaction)
  • Reactome Reaction: HLA-E → PIK3R2 (indirect_complex)
  • Reactome Reaction: B2M → PIK3R2 (indirect_complex)
  • Reactome Reaction: FYN → PIK3R2 (reaction)
  • Reactome Reaction: PIK3CB → IGLC3 (indirect_complex)
  • Reactome Reaction: FCGR2A → PIK3CA (reaction)
  • Reactome Reaction: IGKV4-1 → PIK3CA (indirect_complex)
  • Reactome Reaction: HLA-E → PIK3CB (indirect_complex)
  • Reactome Reaction: FCGR2A → PIK3CB (reaction)
  • Reactome Reaction: B2M → PIK3R2 (reaction)
  • Reactome Reaction: PIK3CA → IGLC1 (indirect_complex)
  • Reactome Reaction: IGHG3 → PIK3R2 (reaction)
  • Reactome Reaction: PIK3R2 → IGLC1 (indirect_complex)
  • Reactome Reaction: CD3G → PIK3R1 (indirect_complex)
  • Reactome Reaction: KLRC2 → PIK3CB (reaction)
  • Reactome Reaction: IGHG1 → PIK3CB (indirect_complex)
  • Reactome Reaction: PIK3R2 → KLRD1 (indirect_complex)
  • Reactome Reaction: KLRC2 → PIK3R2 (indirect_complex)
  • Reactome Reaction: IGKV1-5 → PIK3R1 (reaction)
  • Reactome Reaction: PIK3R1 → IGLC3 (reaction)
  • Reactome Reaction: KLRK1 → PIK3CB (reaction)
  • Reactome Reaction: PIK3R2 → IGLC7 (reaction)
  • Reactome Reaction: FYN → PIK3CB (reaction)
  • Reactome Reaction: IGKV4-1 → PIK3CB (reaction)
  • Reactome Reaction: HLA-E → SYK (indirect_complex)
  • Reactome Reaction: PIK3CB → IGLC7 (indirect_complex)
  • Reactome Reaction: PIK3R2 → IGLC6 (reaction)
  • Reactome Reaction: PIK3R1 → IGLC2 (reaction)
  • Reactome Reaction: LCK → PIK3CB (reaction)
  • Reactome Reaction: LCK → PIK3R1 (indirect_complex)
  • Reactome Reaction: PIK3R1 → IGLC3 (indirect_complex)
  • Reactome Reaction: IGHG4 → PIK3CA (indirect_complex)
  • Reactome Reaction: PIK3CB → IGLC1 (reaction)
  • Reactome Reaction: IGHG4 → PIK3R2 (reaction)
  • Reactome Reaction: PIK3R2 → IGLC6 (indirect_complex)
  • Reactome Reaction: LCK → PIK3CA (indirect_complex)
  • Reactome Reaction: CD247 → PIK3CA (indirect_complex)
  • Reactome Reaction: FCGR3A → PIK3R2 (indirect_complex)
  • Reactome Reaction: PIK3CA → KLRD1 (indirect_complex)
  • Reactome Reaction: FCGR3A → PIK3CB (reaction)
  • Reactome Reaction: HLA-E → PIK3R1 (indirect_complex)
  • Reactome Reaction: PIK3CB → TREM2 (reaction)
  • Reactome Reaction: B2M → PIK3R1 (reaction)
  • Reactome Reaction: KLRC2 → PIK3R1 (reaction)
  • Reactome Reaction: PIK3R2 → TREM2 (indirect_complex)
  • Reactome Reaction: PIK3R1 → KLRD1 (reaction)
  • Reactome Reaction: IGKV1-5 → PIK3CB (reaction)
  • Reactome Reaction: CD3G → PIK3R2 (reaction)
  • Reactome Reaction: KLRK1 → PIK3CA (indirect_complex)
  • Reactome Reaction: LCK → PIK3R2 (indirect_complex)
  • Reactome Reaction: FCGR1A → PIK3CA (indirect_complex)
  • Reactome Reaction: PIK3R1 → IGLC2 (indirect_complex)
  • Reactome Reaction: PIK3R1 → TYROBP (reaction)
  • Reactome Reaction: FCGR3A → PIK3CB (indirect_complex)
  • Reactome Reaction: IGHG3 → PIK3R1 (reaction)
  • Reactome Reaction: SYK → PIK3CB (indirect_complex)
  • Reactome Reaction: PIK3CB → IGLC2 (reaction)
In total, 122 gene pairs are associated to this article in curated databases