Gene interactions and pathways from curated databases and text-mining
Mol Cell Biol 2002, PMID: 11909947

The direct recruitment of BLNK to immunoglobulin alpha couples the B-cell antigen receptor to distal signaling pathways.

Kabak, Shara; Skaggs, Brian J; Gold, Michael R; Affolter, Michael; West, Kelly L; Foster, Mark S; Siemasko, Karyn; Chan, Andrew C; Aebersold, Ruedi; Clark, Marcus R

Following B-cell antigen receptor (BCR) ligation, the cytoplasmic domains of immunoglobulin alpha (Ig alpha) and Ig beta recruit Syk to initiate signaling cascades. The coupling of Syk to several distal substrates requires linker protein BLNK. However, the mechanism by which BLNK is recruited to the BCR is unknown. Using chimeric receptors with wild-type and mutant Ig alpha cytoplasmic tails we show that the non-immunoreceptor tyrosine-based activation motif (ITAM) tyrosines, Y176 and Y204, are required to activate BLNK-dependent pathways. Subsequent analysis demonstrated that BLNK bound directly to phospho-Y204 and that fusing BLNK to mutated Ig alpha reconstituted downstream signaling events. Moreover, ligation of the endogenous BCR induced Y204 phosphorylation and BLNK recruitment. These data demonstrate that the non-ITAM tyrosines of Ig alpha couple Syk activation to BLNK-dependent pathways.

Document information provided by NCBI PubMed

Text Mining Data

BCR → BLNK: " Moreover, ligation of the endogenous BCR induced Y204 phosphorylation and BLNK recruitment "

Manually curated Databases

  • IRef Biogrid Interaction: CD79A — BLNK (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: CD79A — BLNK (direct interaction, pull down)
  • IRef Hprd Interaction: BLNK — CD79A (in vitro)
  • IRef Hprd Interaction: BLNK — CD79A (in vivo)
  • NCI Pathway Database BCR signaling pathway: BLNK (BLNK) → B-cell antigen/BCR complex/LYN/SYK complex (LYN-SYK-CD79B-CD79A) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database BCR signaling pathway: BLNK (BLNK) → B-cell antigen/BCR complex/LYN/SYK/BLNK complex (LYN-SYK-BLNK-CD79B-CD79A) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database BCR signaling pathway: B-cell antigen/BCR complex/LYN/SYK complex (LYN-SYK-CD79B-CD79A) → B-cell antigen/BCR complex/LYN/SYK/BLNK complex (LYN-SYK-BLNK-CD79B-CD79A) (modification, collaborate)
    Evidence: physical interaction
  • Reactome Reaction: CBL → IGLC7 (reaction)
  • Reactome Reaction: CD79B → SH3KBP1 (reaction)
  • Reactome Reaction: SYK → CBLB (reaction)
  • Reactome Reaction: IGKV1-5 → SOS1 (reaction)
  • Reactome Reaction: IGKV4-1 → BLNK (indirect_complex)
  • Reactome Reaction: IGLC3 → IGLC2 (reaction)
  • Reactome Reaction: SYK → IGLC7 (reaction)
  • Reactome Reaction: IGKV4-1 → IGLC1 (reaction)
  • Reactome Reaction: IGKV4-1 → IGLC3 (reaction)
  • Reactome Reaction: CD79A → CD79B (reaction)
  • Reactome Reaction: IGHD → CBLB (reaction)
  • Reactome Reaction: CD79B → IGKC (reaction)
  • Reactome Reaction: CD79A → IGHD (reaction)
  • Reactome Reaction: CD79B → IGLC6 (reaction)
  • Reactome Reaction: GRB2 → IGLC2 (reaction)
  • Reactome Reaction: IGKV1-5 → BLNK (indirect_complex)
  • Reactome Reaction: CD79A → IGHM (reaction)
  • Reactome Reaction: IGHM → IGLC6 (reaction)
  • Reactome Reaction: CBLB → IGLC2 (indirect_complex)
  • Reactome Reaction: GRB2 → IGLC6 (reaction)
  • Reactome Reaction: IGHM → CBLB (reaction)
  • Reactome Reaction: IGHD → SOS1 (reaction)
  • Reactome Reaction: IGHM → IGLC2 (reaction)
  • Reactome Reaction: CD79B → CBLB (indirect_complex)
  • Reactome Reaction: IGKC → IGKV4-1 (reaction)
  • Reactome Reaction: IGHM → IGLC1 (reaction)
  • Reactome Reaction: IGKV4-1 → SOS1 (reaction)
  • Reactome Reaction: IGHM → SH3KBP1 (indirect_complex)
  • Reactome Reaction: IGKC → IGLC6 (reaction)
  • Reactome Reaction: SH3KBP1 → IGLC1 (reaction)
  • Reactome Reaction: IGLC7 → IGLC3 (reaction)
  • Reactome Reaction: IGKV1-5 → IGKV4-1 (reaction)
  • Reactome Reaction: SYK → IGHM (reaction)
  • Reactome Reaction: CD79B → IGLC2 (reaction)
  • Reactome Reaction: IGKC → SYK (reaction)
  • Reactome Reaction: IGKC → IGLC3 (reaction)
  • Reactome Reaction: IGHD → IGLC6 (reaction)
  • Reactome Reaction: SYK → BLNK (reaction)
  • Reactome Reaction: IGKV1-5 → IGLC7 (reaction)
  • Reactome Reaction: IGKV1-5 → CBLB (reaction)
  • Reactome Reaction: CD79A → SH3KBP1 (reaction)
  • Reactome Reaction: BLNK → IGLC6 (indirect_complex)
  • Reactome Reaction: CBL → IGLC1 (reaction)
  • Reactome Reaction: IGLC1 → IGLC1 (reaction)
  • Reactome Reaction: CD79A → IGLC7 (reaction)
  • Reactome Reaction: IGKV1-5 → SH3KBP1 (reaction)
  • Reactome Reaction: CBLB → IGLC3 (indirect_complex)
  • Reactome Reaction: IGLC7 → IGLC2 (reaction)
  • Reactome Reaction: BLNK → IGLC7 (indirect_complex)
  • Reactome Reaction: IGHD → IGLC2 (reaction)
  • Reactome Reaction: IGHM → IGHM (reaction)
  • Reactome Reaction: BLNK → IGLC1 (indirect_complex)
  • Reactome Reaction: IGLC6 → IGLC1 (reaction)
  • Reactome Reaction: SYK → BLNK (indirect_complex)
  • Reactome Reaction: CBL → IGLC6 (indirect_complex)
  • Reactome Reaction: CD79B → CD79B (reaction)
  • Reactome Reaction: IGKC → SH3KBP1 (indirect_complex)
  • Reactome Reaction: SYK → CBLB (indirect_complex)
  • Reactome Reaction: CBL → IGKV1-5 (reaction)
  • Reactome Reaction: SYK → IGLC1 (reaction)
  • Reactome Reaction: IGLC2 → IGLC1 (reaction)
  • Reactome Reaction: IGKV1-5 → SOS1 (indirect_complex)
  • Reactome Reaction: IGHD → SYK (reaction)
  • Reactome Reaction: CBL → SYK (indirect_complex)
  • Reactome Reaction: IGLC6 → IGLC3 (reaction)
  • Reactome Reaction: IGHD → SOS1 (indirect_complex)
  • Reactome Reaction: CD79A → SH3KBP1 (indirect_complex)
  • Reactome Reaction: CD79B → SYK (reaction)
  • Reactome Reaction: SOS1 → IGLC7 (reaction)
  • Reactome Reaction: CD79B → CBL (indirect_complex)
  • Reactome Reaction: IGHD → IGLC7 (reaction)
  • Reactome Reaction: IGKV1-5 → CBLB (indirect_complex)
  • Reactome Reaction: IGHM → IGLC7 (reaction)
  • Reactome Reaction: CD79A → CBL (indirect_complex)
  • Reactome Reaction: CBL → IGLC2 (indirect_complex)
  • Reactome Reaction: SH3KBP1 → IGLC6 (indirect_complex)
  • Reactome Reaction: IGHM → BLNK (reaction)
  • Reactome Reaction: CBLB → IGLC7 (reaction)
  • Reactome Reaction: CD79A → GRB2 (reaction)
  • Reactome Reaction: CBL → IGLC3 (reaction)
  • Reactome Reaction: IGKC → CBLB (reaction)
  • Reactome Reaction: GRB2 → IGLC2 (indirect_complex)
  • Reactome Reaction: CBL → IGHD (indirect_complex)
  • Reactome Reaction: CBL → IGKV4-1 (reaction)
  • Reactome Reaction: SYK → SYK (reaction)
  • Reactome Reaction: SH3KBP1 → IGLC2 (indirect_complex)
  • Reactome Reaction: BLNK → IGLC2 (indirect_complex)
  • Reactome Reaction: GRB2 → IGLC7 (indirect_complex)
  • Reactome Reaction: CD79A → IGLC3 (reaction)
  • Reactome Reaction: CD79A → SOS1 (indirect_complex)
  • Reactome Reaction: SYK → SH3KBP1 (reaction)
  • Reactome Reaction: CBL → IGKC (indirect_complex)
  • Reactome Reaction: SOS1 → IGLC3 (reaction)
  • Reactome Reaction: GRB2 → IGKV1-5 (reaction)
  • Reactome Reaction: CD79A → BLNK (indirect_complex)
  • Reactome Reaction: IGKV4-1 → BLNK (reaction)
  • Reactome Reaction: IGKC → CBLB (indirect_complex)
  • Reactome Reaction: CBL → IGKV1-5 (indirect_complex)
  • Reactome Reaction: SYK → IGLC2 (reaction)
  • Reactome Reaction: SYK → IGLC6 (reaction)
  • Reactome Reaction: CD79B → GRB2 (reaction)
  • Reactome Reaction: CD79B → IGKV1-5 (reaction)
  • Reactome Reaction: IGHM → SOS1 (reaction)
  • Reactome Reaction: SOS1 → IGLC2 (reaction)
  • Reactome Reaction: IGLC7 → IGLC7 (reaction)
  • Reactome Reaction: CBLB → IGLC1 (indirect_complex)
  • Reactome Reaction: SYK → SOS1 (reaction)
  • Reactome Reaction: SH3KBP1 → IGLC6 (reaction)
  • Reactome Reaction: SH3KBP1 → IGLC3 (indirect_complex)
  • Reactome Reaction: SOS1 → IGLC3 (indirect_complex)
  • Reactome Reaction: CD79A → CBLB (indirect_complex)
  • Reactome Reaction: IGHD → GRB2 (reaction)
  • Reactome Reaction: IGKV4-1 → SH3KBP1 (indirect_complex)
  • Reactome Reaction: CD79B → IGLC7 (reaction)
  • Reactome Reaction: CD79A → CBL (reaction)
  • Reactome Reaction: GRB2 → IGKC (reaction)
  • Reactome Reaction: CBL → IGLC7 (indirect_complex)
  • Reactome Reaction: SOS1 → IGLC2 (indirect_complex)
  • Reactome Reaction: IGKV1-5 → IGHM (reaction)
  • Reactome Reaction: CD79A → CBLB (reaction)
  • Reactome Reaction: GRB2 → IGHM (indirect_complex)
  • Reactome Reaction: SH3KBP1 → IGLC7 (reaction)
  • Reactome Reaction: IGHD → IGLC3 (reaction)
  • Reactome Reaction: GRB2 → IGHM (reaction)
  • Reactome Reaction: CD79B → SOS1 (indirect_complex)
  • Reactome Reaction: CD79A → SOS1 (reaction)
  • Reactome Reaction: IGHM → SOS1 (indirect_complex)
  • Reactome Reaction: IGKV4-1 → IGLC2 (reaction)
  • Reactome Reaction: CD79B → GRB2 (indirect_complex)
  • Reactome Reaction: CD79B → IGHM (reaction)
  • Reactome Reaction: BLNK → IGLC3 (indirect_complex)
  • Reactome Reaction: IGKC → SOS1 (indirect_complex)
  • Reactome Reaction: GRB2 → SYK (indirect_complex)
  • Reactome Reaction: GRB2 → IGKV4-1 (indirect_complex)
  • Reactome Reaction: CD79B → SOS1 (reaction)
  • Reactome Reaction: SH3KBP1 → IGLC7 (indirect_complex)
  • Reactome Reaction: SOS1 → IGLC1 (indirect_complex)
  • Reactome Reaction: GRB2 → IGLC7 (reaction)
  • Reactome Reaction: GRB2 → IGKV1-5 (indirect_complex)
  • Reactome Reaction: CD79B → BLNK (reaction)
  • Reactome Reaction: IGKC → BLNK (indirect_complex)
  • Reactome Reaction: IGHM → IGLC3 (reaction)
  • Reactome Reaction: IGKC → IGHM (reaction)
  • Reactome Reaction: CBLB → IGLC3 (reaction)
  • Reactome Reaction: SYK → IGKV4-1 (reaction)
  • Reactome Reaction: GRB2 → IGLC1 (indirect_complex)
  • Reactome Reaction: IGKV4-1 → IGHM (reaction)
  • Reactome Reaction: BLNK → IGLC7 (reaction)
  • Reactome Reaction: GRB2 → IGLC3 (indirect_complex)
  • Reactome Reaction: CBLB → IGLC2 (reaction)
  • Reactome Reaction: SOS1 → IGLC7 (indirect_complex)
  • Reactome Reaction: GRB2 → SYK (reaction)
  • Reactome Reaction: CD79A → IGKV4-1 (reaction)
  • Reactome Reaction: IGHD → IGKV4-1 (reaction)
  • Reactome Reaction: IGLC3 → IGLC3 (reaction)
  • Reactome Reaction: CD79A → SYK (reaction)
  • Reactome Reaction: GRB2 → IGLC1 (reaction)
  • Reactome Reaction: IGKV1-5 → IGLC2 (reaction)
  • Reactome Reaction: IGKC → BLNK (reaction)
  • Reactome Reaction: CD79A → IGKC (reaction)
  • Reactome Reaction: IGHD → IGKV1-5 (reaction)
  • Reactome Reaction: IGHD → SH3KBP1 (indirect_complex)
  • Reactome Reaction: CD79B → CBLB (reaction)
  • Reactome Reaction: GRB2 → IGKV4-1 (reaction)
  • Reactome Reaction: IGHD → CBLB (indirect_complex)
  • Reactome Reaction: IGKV4-1 → IGKV4-1 (reaction)
  • Reactome Reaction: CBL → IGLC2 (reaction)
  • Reactome Reaction: CD79B → CBL (reaction)
  • Reactome Reaction: IGKC → IGKV1-5 (reaction)
  • Reactome Reaction: IGHM → SH3KBP1 (reaction)
  • Reactome Reaction: CBL → IGLC1 (indirect_complex)
  • Reactome Reaction: GRB2 → IGKC (indirect_complex)
  • Reactome Reaction: CBLB → IGLC6 (indirect_complex)
  • Reactome Reaction: IGLC7 → IGLC1 (reaction)
  • Reactome Reaction: CD79A → BLNK (reaction)
  • Reactome Reaction: BLNK → IGLC2 (reaction)
  • Reactome Reaction: CD79A → GRB2 (indirect_complex)
  • Reactome Reaction: SOS1 → IGLC6 (indirect_complex)
  • Reactome Reaction: CBL → IGLC3 (indirect_complex)
  • Reactome Reaction: GRB2 → IGLC6 (indirect_complex)
  • Reactome Reaction: CD79A → IGLC1 (reaction)
  • Reactome Reaction: CD79B → IGLC1 (reaction)
  • Reactome Reaction: IGHD → BLNK (indirect_complex)
  • Reactome Reaction: CBL → IGLC6 (reaction)
  • Reactome Reaction: CD79B → IGKV4-1 (reaction)
  • Reactome Reaction: CD79A → CD79A (reaction)
  • Reactome Reaction: BLNK → IGLC3 (reaction)
  • Reactome Reaction: CBL → SYK (reaction)
  • Reactome Reaction: IGLC6 → IGLC6 (reaction)
  • Reactome Reaction: CD79A → IGKV1-5 (reaction)
  • Reactome Reaction: IGLC2 → IGLC2 (reaction)
  • Reactome Reaction: IGKV4-1 → IGLC7 (reaction)
  • Reactome Reaction: SYK → IGKV1-5 (reaction)
  • Reactome Reaction: IGKC → SOS1 (reaction)
  • Reactome Reaction: SH3KBP1 → IGLC3 (reaction)
  • Reactome Reaction: IGKC → IGKC (reaction)
  • Reactome Reaction: IGKC → IGLC1 (reaction)
  • Reactome Reaction: CBL → IGHM (indirect_complex)
  • Reactome Reaction: SH3KBP1 → IGLC2 (reaction)
  • Reactome Reaction: SH3KBP1 → IGLC1 (indirect_complex)
  • Reactome Reaction: IGHD → IGLC1 (reaction)
  • Reactome Reaction: CBL → IGKV4-1 (indirect_complex)
  • Reactome Reaction: IGHD → IGHM (reaction)
  • Reactome Reaction: IGKV1-5 → BLNK (reaction)
  • Reactome Reaction: CBL → IGHM (reaction)
  • Reactome Reaction: CBLB → IGLC6 (reaction)
  • Reactome Reaction: BLNK → IGLC6 (reaction)
  • Reactome Reaction: IGKC → IGLC2 (reaction)
  • Reactome Reaction: GRB2 → IGLC3 (reaction)
  • Reactome Reaction: IGKV4-1 → SOS1 (indirect_complex)
  • Reactome Reaction: IGKV1-5 → IGLC6 (reaction)
  • Reactome Reaction: CD79B → SH3KBP1 (indirect_complex)
  • Reactome Reaction: CBLB → IGLC1 (reaction)
  • Reactome Reaction: IGHD → IGKC (reaction)
  • Reactome Reaction: CD79B → BLNK (indirect_complex)
  • Reactome Reaction: IGHM → BLNK (indirect_complex)
  • Reactome Reaction: CD79A → IGLC6 (reaction)
  • Reactome Reaction: IGKV4-1 → SH3KBP1 (reaction)
  • Reactome Reaction: IGKV1-5 → IGLC1 (reaction)
  • Reactome Reaction: IGKV1-5 → IGKV1-5 (reaction)
  • Reactome Reaction: IGHM → CBLB (indirect_complex)
  • Reactome Reaction: CD79A → IGLC2 (reaction)
  • Reactome Reaction: IGHD → GRB2 (indirect_complex)
  • Reactome Reaction: IGLC3 → IGLC1 (reaction)
  • Reactome Reaction: SYK → IGLC3 (reaction)
  • Reactome Reaction: CD79B → IGLC3 (reaction)
  • Reactome Reaction: SYK → SOS1 (indirect_complex)
  • Reactome Reaction: IGHD → IGHD (reaction)
  • Reactome Reaction: CBL → IGHD (reaction)
  • Reactome Reaction: SYK → SH3KBP1 (indirect_complex)
  • Reactome Reaction: SOS1 → IGLC1 (reaction)
  • Reactome Reaction: IGKV4-1 → CBLB (reaction)
  • Reactome Reaction: IGLC6 → IGLC2 (reaction)
  • Reactome Reaction: CBLB → IGLC7 (indirect_complex)
  • Reactome Reaction: IGHD → SH3KBP1 (reaction)
  • Reactome Reaction: IGKV1-5 → SH3KBP1 (indirect_complex)
  • Reactome Reaction: BLNK → IGLC1 (reaction)
  • Reactome Reaction: IGKC → SH3KBP1 (reaction)
  • Reactome Reaction: IGKV1-5 → IGLC3 (reaction)
  • Reactome Reaction: IGLC7 → IGLC6 (reaction)
  • Reactome Reaction: IGHD → BLNK (reaction)
  • Reactome Reaction: CBL → IGKC (reaction)
  • Reactome Reaction: CD79B → IGHD (reaction)
  • Reactome Reaction: IGKV4-1 → CBLB (indirect_complex)
  • Reactome Reaction: SOS1 → IGLC6 (reaction)
  • Reactome Reaction: IGKC → IGLC7 (reaction)
  • Reactome Reaction: IGKV4-1 → IGLC6 (reaction)
In total, 175 gene pairs are associated to this article in curated databases