Journal of Cell Science, Vol 107, Issue 2 613-620, Copyright © 1994 by Company of Biologists

JOURNAL ARTICLES

Nuclear import of the myogenic factor MyoD requires cAMP-dependent protein kinase activity but not the direct phosphorylation of MyoD

M Vandromme, G Carnac, C Gauthier-Rouviere, D Fesquet, N Lamb and A Fernandez
Cell Biology Unit, CRBM, CNRS-INSERM, Montpellier, France.

MyoD is a nuclear phosphoprotein that belongs to the family of myogenic regulatory factors and acts in the transcriptional activation of muscle-specific genes. We have investigated the role of cAMP-dependent protein kinase (A-kinase) in modulating the nuclear locale of MyoD. Purified MyoD protein microinjected into the cytoplasm of rat embryo fibroblasts is rapidly translocated into the nucleus. Inhibition of A-kinase activity through injection of the specific inhibitory peptide PKI prevents this nuclear localisation. This inhibition of nuclear location is specifically reversed by injection of purified A-kinase catalytic subunit, showing the requirement for A-kinase in the nuclear import of MyoD. Site-directed mutagenesis of all the putative sites for A-kinase-dependent phosphorylation on MyoD, substituting serine or threonine residues for the non-phosphorylatable amino acid alanine, had no effect on nuclear import of mutated MyoD. These data exclude the possibility that the effect of A-kinase on the nuclear translocation of MyoD is mediated by direct phosphorylation of MyoD and imply that A-kinase operates through phosphorylation of components involved in the nuclear transport of MyoD.

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