The myogenic kinome: protein kinases critical to mammalian skeletal myogenesis

Abstract

Myogenesis is a complex and tightly regulated process, the end result of which is the formation of a multinucleated myofibre with contractile capability. Typically, this process is described as being regulated by a coordinated transcriptional hierarchy. However, like any cellular process, myogenesis is also controlled by members of the protein kinase family, which transmit and execute signals initiated by promyogenic stimuli. In this review, we describe the various kinases involved in mammalian skeletal myogenesis: which step of myogenesis a particular kinase regulates, how it is activated (if known) and what its downstream effects are. We present a scheme of protein kinase activity, similar to that which exists for the myogenic transcription factors, to better clarify the complex signalling that underlies muscle development.

Targeting cAMP/PKA pathway for glycemic control and type 2 diabetes therapy

“…Signals via cAMP/PKA pathway control the development (Chen et al 2005a, Knight & Kothary 2011) and metabolism (Berdeaux & Stewart 2012) of skeletal muscle, which plays an essential role in the regulation of glucose homeostasis (Stump et al 2006). As mentioned above, liver and skeletal muscle are the major sites for glycogen storage.…”

Co-ingestion of carbohydrate with branched-chain amino acids or l-leucine does not preferentially increase serum IGF-1 and expression of myogenic-related genes in response to a single bout of resistance exercise

“…The expansion of activated satellite cells occurs from myogenic factor 5 (myf5). Myoblast determination protein (Myo-D) is involved in determining the differentiation poteintial of an activated myoblast and acts together with myogenin to drive differentiation, whereas muscle-specific regulatory factor 4 (MRF-4) is required for hypertrophy as it plays a role in the maturation of myotubes (Knight & Kothary, 2011).…”

“…Cyclin D, a G 1 cyclin which regulates progression through G 1 and entry into the S phase of the cell cycle, is responsible for its role in myoblast differentiation by activating CDK2 (Knight & Kothary, 2011). For myoblasts to differentiate, the cell cyle must be exited and the restraints the CDKs place on differentitation must be removed.…”

“…The CIP/KIPs, p21cip and p27kip, inhibit all G1 CDKs (Knight & Kothary, 2011). Furthermore, myostatin which is a member of the transforming growth factor beta (TGF-β) family works in a paracrine/autocrine manner through the activin IIB receptor (ACTRIIB), and is a negative regulator of myogenesis and subsequent muscle protein accretion by repressing the expression of Myo-D, myogenin, myf5, and p21cip, and by down-regulating cyclin D1 during the G 1 phase of the cell cycle (Langley et al 2002).…”

Skeletal muscle development in vertebrate animals

“…The timing of different developmental stages varied significantly but the end products are same to form multinucleated myofibers with contractile capability (Knight and Kothary, 2011). Myogenesis is controlled by an elaborate interplay of extrinsic and intrinsic regulatory mechanisms (Bentzinger et al, 2012) regulated by myogenic regulatory factors including 2-3 distinct phases, in addition, protein kinase family which transmits and executes signals originated by promyogenic stimuli (Rehfeldt et al, 2011a andKnight andKothary, 2011).…”