The myogenic kinome: protein kinases critical to mammalian skeletal myogenesis

Embryonic myogenesis is a multistep process that begins with the commitment of an embryonic precursor to the myogenic lineage, followed by the proliferation of these committed myoblasts, the differentiation of myoblasts into postmitotic myocytes, and finally fusion of myocytes to form a multinucleated myotube. As the myotube matures, the syncytial cell becomes specialized for its particular function, with the bulk of the cytoplasm occupied by the contractile apparatus, and where the myotube/myofibre can further grow or hypertrophy in response to appropriate stimuli. Postnatal myogenesis is a similar process, except that fusion occurs primarily between myoblasts and preexisting myotubes, and where the role of the embryonic precursor is played by the quiescent satellite cell.The process of myogenesis is controlled by several myogenic transcription factors that act as terminal effectors of signalling cascades and produce appropriate developmental stage-specific transcripts. The concerted roles that these transcription factors play is well known and well reviewed (see, for example, Sabourin and Rudnicki [1] and Le Grand and Rudnicki [2]). Paired-box protein 7 (Pax7) maintains a population of quiescent satellite cells and, together with myogenic factor 5 (Myf5), plays a role in the expansion of activated myoblasts. Myoblast determination protein (MyoD) is believed to determine the differentiation potential of an activated myoblast, and acts together with myogenin and myocyte enhancer factor 2 (MEF2) to drive differentiation. Finally, muscle-specific regulatory factor 4 (MRF4) is required for hypertrophy, although it may have other roles as well. Obviously, these transcription factors do not act alone, but exist as part of complex signalling cascades that control every stage of myogenesis. One of the major components of these cascades is the protein kinase, an enzyme that directs cell behaviour through the simple but reversible process of phosphorylation. Over 500 kinases