[Function of HS1 protein in B-cell antigen-receptor signaling and induction of apoptosis]

Cross-linking of antigen receptor complex on the surface of B cells induces activation of the associated protein-tyrosine kinases (PTKs) which, in turn, phosphorylate and activate a variety of intracellular proteins, some of those are known to transmit the signal to further downstream. In some circumstances, such signals eventually result in apoptosis, rather than proliferation, of the cells. The programmed B-cell death is thought to be crucial in developmental selection of functional cells, self-tolerance, regulation of immune response, and so on. Molecular mechanisms of the intracellular signaling pathways leading to the apoptosis are still obscure. HS1, a hematopoietic-lineage specific protein, is a major substrate of the antigen-receptor associated PTKs. The biochemical and predicted structural features suggest HS1 actively involves in the signal transduction pathway from the antigen receptors and may directly regulate a gene transcription. In this review article, discussed are the roles of non-receptor type tyrosine kinases and HS1 in the pathway leading to apoptosis of B cells, recently evidenced by cell- and mouse-genetics.