Suppressive effect of transforming growth factor-beta on the phosphorylation of endogenous substrates by conventional and novel protein kinase C in primary cultured mouse epidermal cells.
The effect of transforming growth factor-beta (TGF-beta) on the endogenous protein phosphorylation caused by phorbol 12-myristate 13-acetate (PMA), a potent activator of protein kinase C (PKC), was examined in primary cultured mouse epidermal cells. PMA markedly stimulates phosphorylation of endogenous proteins, i.e. KP-1 and KP-2, through Ca(2+)-dependent conventional PKC (cPKC), and KP-10 through Ca(2+)-independent novel PKC (nPKC) in intact epidermal cells. TGF-beta strongly suppressed the PMA-stimulated phosphorylation of these three proteins. Rate of dephosphorylation of these phosphorylated proteins was not affected by TGF-beta. Treatment of epidermal cells with TGF-beta decreased cPKC activity both in cytosolic and particulate fractions, but not nPKC activity. These results indicate that TGF-beta suppresses cPKC- and nPKC-mediated endogenous protein phosphorylation in intact epidermal cells, but the mechanisms of suppression are different.
Nishikawa
K
K
Department of Pharmacology, School of Medicine, Keio University, Tokyo, Japan.
Yamamoto
S
S
Nagumo
H
H
Otsuka
C
C
Kato
R
R
D000818:Animals; D002478:Cells, Cultured; D004817:Epidermis / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D013379:Substrate Specificity; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D011506:Proteins; D016212:Transforming Growth Factor beta; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate