Differential regulation of p34cdc2 and p33cdk2 by transforming growth factor-β1 in murine mammary epithelial cells

✍ Scribed by Michael P. Fautsch; Scott T. Eblen; Robert A. Anders; Rebekah J. Burnette; Edward B. Leof Dr.

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 961 KB
• Volume: 58
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.240580415

✦ Synopsis

Cyclin-dependent kinases (cdks) are a family of proteins whose function plays a critical role in cell cycle traverse. Transforming growth factor+, (TGF-P 1) is a potent growth inhibitor of epithelial cells. Since cdks have been suggested as possible biochemical markers for TGF-@ growth inhibition, we investigated the effect of TGF-P, on cdc2 and cdk2 in a normal mouse mammary epithelial cell line (MME) and a TGF-@-resistant MME cell line (BG18.2). TGF-P, decreases newly synthesized cdc2 protein levels within 6 h after addition. Coincident with this decrease in newly synthesized cdc2 protein was a marked reduction in its ability to phosphorylate histone HI. This decrease in kinase activity is not due to a change in steady-state levels of cdc2 protein, since mRNA and total protein levels of cdc2 are not reduced until 12 'h after TGF-P1 addition. This suggests that the kinase activity of cdc2 is dependent on newly synthesized cdc2 protein. Moreover, the protein synthesis of another cyclin-dependent kinase, cdk2, is not effected by TGF-PI addition, but its kinase activity is substantially reduced. Thus, it appears that TGF-P decreases the kinase activity of both cdc2 and cdk2 by distinct mechanisms. D 1995 WiIey-Liss, ~n c .