REGULATION OF P56LCK KINASE EXPRESSION AND CONTROL OF DNA-SYNTHESIS IN ACTIVATED HUMAN B-LYMPHOCYTES

In this study, we analyzed the expression and regulation of src kinase p56lck expression during human B lymphocyte activation. We show that upon mitogenic stimulation with anti-IgM antibodies and interleukin-2, specific mRNA for p56lck becomes detectable in B cells after 24 h of activation and is followed by an increase in p56lck protein expression on days 2 and 3. This up-regulation is specific for p56lck since expr ession of other src kinases such as fyn, lyn, or yes was not modified. Furthermore, immune complex kinase assays show that p56lck protein ex pressed on day 2 is associated with kinase activity. Experiments using lck-specific antisense oligonucleotides show that the G0-G1 transitio n does not require p56lck, whereas DNA synthesis is dependent upon its expression. Thus, our data demonstrate that p56lck expression is up-r egulated during human B cell stimulation and this kinase plays an impo rtant role during the control of late steps of B lymphocyte activation such as S phase entry.