Integrin signaling at the M/G1 transition induces expression of cyclin E

The activities of the mammalian G1 cyclins, cyclin D and cyclin E, during c ell cycle progression (G1/S) are believed to be regulated by cell attachmen t and the presence of growth factors. In order to study the importance of c ell attachment and concomitant integrin signaling on the expression of G1 c yclins during the natural adhesion process from mitosis to interphase, prot ein expression was monitored in cells that were synchronized by mitotic sha ke off. Here we show that in Chinese hamster ovary (CHO) and neuroblastoma (N2A) cells, expression of cyclin E at the M/G1 transition is regulated by both growth factors and cell attachment, while expression of cyclin D seems to be entirely dependent on the presence of serum. Expression of cyclin E appears to be correlated with the phosphorylation of the retinoblastoma pro tein, suggesting a link with the activity of the cyclin D/cdk4 complex. Exp ression of the cdk inhibitors p21(cip1/Waf1) and p27(Kip1) is not changed u pon serum depletion or detachment of cells during early G1, suggesting no d irect role for these CKIs in the regulation of cyclin activity. Although in hibition of cyclin E/cdk2 kinase activity has been reported previously, thi s is the first time that cyclin E expression is shown to be dependent on ce ll attachment. (C) 1999 Academic Press.