THE DIFFERENTIAL CATALYTIC ACTIVITY OF ALTERNATIVELY SPLICED CDK2-ALPHA AND CDK2-BETA IN THE G(1) S TRANSITION AND EARLY S-PHASE/

Progression through the G(1)/S transition of the cell cycle is regulat ed by cyclin E/cdk2 and cyclin A/cdk2 complexes, We demonstrate that t here are two forms of murine cdk2, (cdk2 alpha and beta), Cdk2 alpha c onsist of 298 amino acids, while cdk2 beta contains a 48-amino-acid in sert between Met (196) and Val (197) of cdk2 alpha, Cdk2 beta results from differential splicing of the primary RNA transcript of the cdk2 g ene. Although human cdk2 genomic DNA contained the sequence of the ins ert for the beta form, cdk2 beta was not detected by either Western bl ot or RT-PCR in human T-cells or several other human cell lines, Cdk2 beta expression in murine cells was similar to that of the phosphoryla ted, catalytically active form of cdk2 alpha. Cdk2 alpha and cdk2 beta have very similar binding activity to cyclin E and to the cdk inhibit or p27(KipI), The alternatively spliced cdk2 beta possesses catalytic activity in vivo and in vitro, The differential catalytic activity of these two forms of cdk2, suggests that cdk2 alpha and cdk2 beta may pe rform different functions at or near the G(1)/S transition and early S phase. (C) 1998 Academic Press.