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

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.

Pubmed ID: 11909947

Authors

  • Kabak S
  • Skaggs BJ
  • Gold MR
  • Affolter M
  • West KL
  • Foster MS
  • Siemasko K
  • Chan AC
  • Aebersold R
  • Clark MR

Journal

Molecular and cellular biology

Publication Data

April 22, 2002

Associated Grants

  • Agency: NIAID NIH HHS, Id: AI42787
  • Agency: NIGMS NIH HHS, Id: GM52736
  • Agency: NIGMS NIH HHS, Id: GM56187
  • Agency: NHLBI NIH HHS, Id: HL07065

Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Antigens, CD
  • Antigens, CD79
  • Carrier Proteins
  • Clone Cells
  • Enzyme Precursors
  • Intracellular Signaling Peptides and Proteins
  • Isoenzymes
  • Mice
  • Models, Molecular
  • Mutation
  • Phospholipase C gamma
  • Phosphoproteins
  • Protein-Tyrosine Kinases
  • Receptor, Platelet-Derived Growth Factor beta
  • Receptors, Antigen, B-Cell
  • Recombinant Fusion Proteins
  • Signal Transduction
  • Type C Phospholipases
  • src Homology Domains