Dual role of the tyrosine activation motif of the Ig-alpha protein during signal transduction via the B cell antigen receptor

EMBO J. 1994 Jan 1;13(1):83-9.

Abstract

The B cell antigen receptor (BCR) is a multimeric protein complex consisting of the ligand binding immunoglobulin molecule and the Ig-alpha/beta heterodimer that mediates intracellular signalling by coupling the receptor to protein tyrosine kinases (PTKs). Transfection of the Ig-alpha deficient myeloma cell line J558L microns with expression vectors coding for mutated Ig-alpha allowed us to test the function of the tyrosines in the cytoplasmic region of Ig-alpha in the context of the BCR. Furthermore we expressed Ig-alpha mutations as chimeric CD8-Ig-alpha molecules on K46 B lymphoma cells and tested their signalling capacity in terms of PTK activation and release of calcium. We show here that the conserved tyrosine residues in the cytoplasmic portion of Ig-alpha have a dual role. First, they are required for efficient activation of PTKs during signal induction and second, one of them is subject to phosphorylation by activated src-related PTKs. Phosphorylation on tyrosine in the cytoplasmic portion of Ig-alpha is discussed as a possible mechanism to couple the BCR to SH2 domain-carrying molecules.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, CD / chemistry
  • Antigens, CD / metabolism*
  • Base Sequence
  • CD79 Antigens
  • Cell Line
  • DNA
  • Mice
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Phosphorylation
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-fyn
  • Receptors, Antigen, B-Cell / chemistry
  • Receptors, Antigen, B-Cell / metabolism*
  • Sequence Homology, Amino Acid
  • Signal Transduction*
  • Transfection
  • Tyrosine / metabolism*

Substances

  • Antigens, CD
  • CD79 Antigens
  • Cd79a protein, mouse
  • Proto-Oncogene Proteins
  • Receptors, Antigen, B-Cell
  • Tyrosine
  • DNA
  • Protein-Tyrosine Kinases
  • Fyn protein, mouse
  • Proto-Oncogene Proteins c-fyn