CALMODULIN REGULATES THE EXPRESSION OF CDKS, CYCLINS AND REPLICATIVE ENZYMES DURING PROLIFERATIVE ACTIVATION OF HUMAN T-LYMPHOCYTES

Cell cycle is regulated by the activation of complexes of cyclins and cyclin-dependent protein kinases at specific points. Quiescent cells l ack both cyclins and cyclin-dependent kinases but their expression is induced after proliferative activation. Cyclin A/cdk2 complexes are in volved in the onset of DNA replication whereas cyclin B/cdc2 trigger m itosis. We report here that Ca2+ and calmodulin regulate the expressio n of cdk2, cdc2, cyclin B and the proliferating cell nuclear antigen ( a co-factor of DNA polymerase-delta) in human T lymphocytes. Likewise, the expression of cdk4, cyclin A and DNA polymerase-a is dependent of the sinergistic effect of both the Ca2+/calmodulin and the protein ki nase C pathways. Thus, calmodulin controls DNA synthesis by regulating the levels of cdk2 and proliferating cell nuclear antigen and mitosis entry by modulating the expression of cyclin B and cdc2. (C) 1994 Aca demic Press, Inc.