Distinct mechanisms mediate SHC association with the activated and resting B cell antigen receptor

Eur J Immunol. 1996 Aug;26(8):1960-5. doi: 10.1002/eji.1830260842.

Abstract

Ligation of the B cell antigen receptor (BCR) complex initiates tyrosine phosphorylation of the receptor's transducer components, Ig-alpha and Ig-beta and tyrosine kinase-dependent accumulation of GTP-bound, activated p21ras. The mechanism of receptor coupling to p21ras activation and the roles of Ig-alpha and Ig-beta are unknown. The results reported here indicate that the resting, nonphosphorylated BCR associates with the Grb-2/Sos-linker SHC via the Ig-alpha immunoreceptor-based tyrosine activation motif (ITAM). Ig-alpha specificity of this interaction is determined by the sequence DCSM found in Ig-alpha, but not Ig-beta. Tyrosine phosphorylation of Ig-alpha and Ig-beta ITAM allows recruitment of SHC, which now binds directly to both Ig-alpha and Ig-beta via a phosphotyrosine/SH2 interaction. In confirmation of recent studies by Saxton et al. (J. Immunol. 1994. 153: 623) receptor ligation leads to tyrosine phosphorylation of SHC and to the formation of a phospho-SHC/Grb2/Sos complex. In view of previous studies which demonstrated p21ras co-capping with ligated BCR, the data presented here suggest that Ig-alpha/beta- and SHC tyrosine phosphorylation-dependent recruitment of the Grb2/Sos complex to the receptor can occur and may provide a mechanism by which the nucleotide exchange activity of Sos could mediate activation of BCR-localized p21ras.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Amino Acid Sequence
  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism*
  • ErbB Receptors / metabolism
  • GRB2 Adaptor Protein
  • Interphase / immunology*
  • Lymphocyte Activation*
  • Mice
  • Molecular Sequence Data
  • Phosphorylation
  • Protein Binding / immunology
  • Protein-Tyrosine Kinases / metabolism
  • Proteins / metabolism
  • Receptors, Antigen, B-Cell / chemistry
  • Receptors, Antigen, B-Cell / metabolism*
  • Tumor Cells, Cultured
  • Tyrosine / metabolism
  • src Homology Domains*

Substances

  • Adaptor Proteins, Signal Transducing
  • GRB2 Adaptor Protein
  • Grb2 protein, mouse
  • Proteins
  • Receptors, Antigen, B-Cell
  • Tyrosine
  • ErbB Receptors
  • Protein-Tyrosine Kinases