The inhibition of differentiation caused by TGFbeta in fetal myoblasts is dependent upon selective expression of PKCtheta: a possible molecular basis for myoblast diversification during limb histogenesis.
Embryonic and fetal skeletal myoblasts are responsible for the formation 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 growth factor beta and phorbol esters. Thus, differential expression of specific molecules involved in the transduction of extracellular signals may contribute to the different phenotypes. We report here that protein kinase C theta, but none of the other known protein kinase C isoforms, is selectively expressed in fetal and postnatal muscle cells (at both the myoblast and myotube stage) in vitro and in vivo. By contrast, embryonic myoblasts and myotubes do not express protein kinase C theta in vitro or in vivo. This difference is causally related to a differential response to transforming growth factor beta, since overexpression of protein kinase C theta, but not of protein kinase C alpha or zeta, in embryonic myoblasts makes these cells sensitive to transforming growth factor beta. These data demonstrate for the first time that a protein kinase C isoform is a key component of the signal transduction cascade which follows exposure of myoblasts to transforming growth factor beta. They also suggest a specific role for protein kinase C theta in determining the fate of different myoblasts during muscle histogenesis.
Zappelli
F
F
Institute of Histology and General Embryology, University of Rome La Sapienza, Italy.
Willems
D
D
Osada
S
S
Ohno
S
S
Wetsel
W C
WC
Molinaro
M
M
Cossu
G
G
Bouché
M
M
D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D005314:Embryonic and Fetal Development; D005121:Extremities / Q000196:embryology; D018507:Gene Expression Regulation, Developmental; D007527:Isoenzymes / Q000032:analysis / Q000096:biosynthesis* / Q000737:chemistry; D051379:Mice; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000166:cytology* / Q000187:drug effects / Q000196:embryology*; D009928:Organ Specificity; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D011493:Protein Kinase C / Q000032:analysis / Q000096:biosynthesis* / Q000737:chemistry; D000074121:Protein Kinase C-theta; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D007527:Isoenzymes; D010446:Peptide Fragments; D016212:Transforming Growth Factor beta; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta; D013755:Tetradecanoylphorbol Acetate