Mp. Fautsch et al., DIFFERENTIAL REGULATION OF P34(CDC2) AND P33(CDK2) BY TRANSFORMING GROWTH FACTOR-BETA(1) IN MURINE MAMMARY EPITHELIAL-CELLS, Journal of cellular biochemistry, 58(4), 1995, pp. 517-526
Cyclin-dependent kinases (cdks) are a family of proteins whose functio
n plays a critical role in cell cycle traverse. Transforming growth fa
ctor-beta(1) (TGF-beta 1) is a potent growth inhibitor of epithelial c
ells. Since cdks have been suggested as possible biochemical markers f
or TCF-beta growth inhibition, we investigated the effect of TGF-beta(
1) on cdc2 and cdk2 in a normal mouse mammary epithelial cell line (MM
E) and a TGF-beta-resistant MME cell line (BG18.2). TGF-beta(1) decrea
ses newly synthesized cdc2 protein levels within 6 h after addition. C
oincident with this decrease in newly synthesized cdc2 protein was a m
arked reduction in its ability to phosphorylate histone H1. This decre
ase in kinase activity is not due to a change in steady-state levels o
f cdc2 protein, since mRNA and total protein levels of cdc2 are not re
duced until 12 h after TGF-beta(1) addition. This suggests that the ki
nase activity of cdc2 is dependent on newly synthesized cdc2 protein.
Moreover, the protein synthesis of another cyclin-dependent kinase, cd
k2, is not effected by TGF-beta(1) addition, but its kinase activity i
s substantially reduced. Thus, it appears that TGF-beta decreases the
kinase activity of both cdc2 and cdk2 by distinct mechanisms. (C) 1995
Wiley-Liss, Inc.