Histone phosphorylation in phorbol ester stimulated and beta-adrenergically stimulated mouse epidermis in vivo and characterization of an epidermal protein phosphorylation system.

Under certain physiological conditions a change in the phosphorylation of histones in mouse epidermis in vivo was observed. Thus a single local application of the tumor-promoting mitogen 12-O-tetradecanoylphorbol-13-acetate caused a long-lasting increase of histone H1 phosphorylation which paralleled stimulated cell proliferation. Injection of the antimitotic beta-adrenergic agonist isoproterenol led to a temporary decrease in the rate of phosphorylation of H1, H2A and H2B immediately after cyclic AMP accumulation. A complete protein phosphorylation system could be demonstrated in mouse epidermis homogenates. The following enzyme activities were partially purified and characterized: a cyclic AMP-dependent histone kinase; a 'casein kinase' and an 'unspecific' protein kinase; a histone-specific protein phosphatase; and two 'unspecific' phosphoprotein phosphatases. In addition, a stimulatory effect of cyclic GMP on histone phosphorylation was observed. The enzymes were found to be predominantly localized in the 105000 X g supernatant, but a small proportion of protein kinase and phosphatase activity could be regularly demonstrated in cell nuclei.