RESTORATION OF SURFACE IGM-MEDIATED APOPTOSIS IN AN ANTI-IGM-RESISTANT VARIANT OF WEHI-231 LYMPHOMA-CELLS BY HS1, A PROTEIN-TYROSINE KINASESUBSTRATE

The HS1 protein is one of the major substrates of non-receptor-type pr otein-tyrosine kinases and is phosphorylated immediately after crossli nking of the surface IgM on B cells. The mouse B-lymphoma cell line WE HI-231 is known to undergo apoptosis upon crosslinking of surface IgM by anti-IgM antibodies. Variants of WEHI-231 that were resistant to an ti-IgM-induced apoptosis expressed dramatically reduced levels of HS1 protein. Expression of the human HS1 protein from an expression vector introduced into one of the variant cell lines restored the sensitivit y of the cells to apoptosis induced by surface IgM crosslinking. These results suggest that HS1 protein plays a crucial role in the B-cell a ntigen receptor-mediated signal transduction pathway that leads to apo ptosis.