THE INHIBITION OF DIFFERENTIATION CAUSED BY TGF-BETA IN FETAL MYOBLASTS IS DEPENDENT UPON SELECTIVE EXPRESSION OF PKC-THETA - A POSSIBLE MOLECULAR-BASIS FOR MYOBLAST DIVERSIFICATION DURING LIMB HISTOGENESIS

Embryonic and fetal skeletal myoblasts are responsible for the formati on of primary and secondary fibers in mammals, but the mechanism which diversifies their fate is unknown. In vitro, embryonic myoblasts are resistant to the differentiation inhibitory effects of transforming gr owth factor beta and phorbol esters. Thus, differential expression of specific molecules involved in the transduction of extracellular signa ls may contribute to the different phenotypes. We report here that pro tein kinase C theta, but none of the other known protein kinase C isof orms, is selectively expressed in fetal and postnatal muscle cells (at both the myoblast and myotube stage) in vitro and in vivo. By contras t, embryonic myoblasts and myotubes do not express protein kinase C th eta in vitro or in vivo. This difference is causally related to a diff erential response to transforming growth factor beta, since overexpres sion of protein kinase C theta, but not of protein kinase C alpha or z eta, in embryonic myoblasts makes these cells sensitive to transformin g growth factor beta. These data demonstrate for the first time that a protein kinase C isoform is a key component of the signal transductio n cascade which follows exposure of myoblasts to transforming growth f actor beta. They also suggest a specific role for protein kinase C the ta in determining the fate of different myoblasts during muscle histog enesis. (C) 1996 Academic Press, Inc.