IDENTIFICATION OF HS1 PROTEIN AS A MAJOR SUBSTRATE OF PROTEIN-TYROSINE KINASE(S) UPON B-CELL ANTIGEN RECEPTOR-MEDIATED SIGNALING

Crosslinking of membrane-bound immunoglobulins, which are B-cell antig en receptors, causes proliferation and differentiation of B cells or i nhibition of their growth. The receptor-mediated signaling involves ty rosine phosphorylation of cellular proteins and rapid activation of Sr c-like kinases. The amino acid sequences of rive proteolytic peptides of p75, a major substrate of protein-tyrosine kinase(s) in the signali ng, showed that p75 is the human HS1 gene product. The HS1 gene is exp ressed specifically in hematopoietic cells and encodes p75HS1, which c arries both helix-turn-helix and Src homology 3 motifs. p75HS1 showed rapid tyrosine phosphorylation and association with a Src-like kinase, Lyn, after crosslinking of membrane-bound IgM. Thus, p75HS1 may be an important substrate of Lyn and possibly other protein-tyrosine kinase s upon B-cell antigen receptor-mediated signaling.