The myogenic kinome: Protein kinases critical to mammalian skeletal myogenesis

Regenerative Medicine Program, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON, K1H 8L6, Canada. .
Skeletal Muscle 09/2011; 1(1):29. DOI: 10.1186/2044-5040-1-29
Source: PubMed


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.

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Available from: Rashmi Kothary,
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    • "This process involves various enzymes and transcription factors, including myod and myf5, which activate, proliferate, or differentiate muscle fibers during deposition (Johnston 2006; Knight and Kothary 2011). Further growth of muscle mass then occurs through hypertrophy (Johnston 2006; Knight and Kothary 2011), and in fish, postnatal muscle growth can also occur through hyperplasia (Johnston et al. 2011). Therefore, we selected a representative set of genes to examine these major processes. "
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    ABSTRACT: Growth hormone (GH) transgenic salmon possesses markedly increased metabolic rate, appetite, and feed conversion efficiency, as well as an increased ability to compete for food resources. Thus, the ability of GH-transgenic fish to withstand periods of food deprivation as occurs in nature is potentially different than that of nontransgenic fish. However, the physiological and genetic effects of transgenic GH production over long periods of food deprivation remain largely unknown. Here, GH-transgenic coho salmon (Oncorhynchus kisutch) and nontransgenic, wild-type coho salmon were subjected to a 3-month food deprivation trial, during which time performance characteristics related to growth were measured along with proximate compositions. To examine potential genetic effects of GH-transgenesis on long-term food deprivation, a group of genes related to muscle development and liver metabolism was selected for quantitative PCR analysis. Results showed that GH-transgenic fish lose weight at an increased rate compared to wild-type even though proximate compositions remained relatively similar between the groups. A total of nine genes related to muscle physiology (cathepsin, cee, insulin-like growth factor, myostatin, murf-1, myosin, myogenin, proteasome delta, tumor necrosis factor) and five genes related to liver metabolism (carnitine palmitoyltransferase, fatty acid synthase, glucose-6-phosphatase, glucose-6-phosphate dehydrogenase, glucokinase) were shown to be differentially regulated between GH-transgenic and wild-type coho salmon over time. These genetic and physiological responses assist in identifying differences between GH-transgenic and wild-type salmon in relation to fitness effects arising from elevated growth hormone during periods of long-term food shortage.
    Marine Biotechnology 08/2015; DOI:10.1007/s10126-015-9654-8 · 3.27 Impact Factor
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    • "It has also been shown that HGF regulates proliferation rates via signalling through SHP2, a protein tyrosine phosphatase that mediates MAPK activity; these proliferation rates were dependent on the HGF dose utilized (Chazaud, 2010; Li et al., 2009). MAPKs are thought to be more intensively involved in regulating cell proliferation, differentiation and cell migration, while signaling through PI3K mediates cell survival and resistance to apoptosis (Faria et al., 2011; Keren et al., 2005; Knight & Kothary, 2011; Li et al., 2000; Lluis et al., 2006; Organ & Tsao, 2011). "
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    ABSTRACT: Hepatocyte growth factor (HGF) regulates satellite cell activation, proliferation, and differentiation. We analyzed the dose-dependent effects of HGF on myogenesis. Murine C2C12 and human donor-derived skeletal muscle myoblasts were treated with 0, 2, or 10 ng/ml HGF followed by assessment of proliferation and differentiation. HGF (2 ng/ml) significantly promoted cell division, but reduced myogenic commitment and fusion. Conversely, 10 ng/ml HGF reduced proliferative capability, but increased differentiation. c-Met expression analysis revealed significantly decreased expression in differentiating cells cultured with 2 ng/ml HGF, but increased expression in proliferating cells with 10 ng/ml HGF. Mitogen-activated protein kinase (MAPKs: ERK, JNK, or p38K) and phosphatidylinositol-3-kinase (PI3K) inhibition abrogated the HGF-stimulated increase in cell number. Interestingly, PI3K and p38 kinase facilitated the negative effect of HGF on proliferation, while ERK inhibition abrogated the HGF-mediated decrease in differentiation. Dose-dependent effects of HGF are mediated by changes in c-Met expression and downstream MAPK and PI3K signalling.
    Growth factors (Chur, Switzerland) 07/2015; 33(3):1-13. DOI:10.3109/08977194.2015.1058260 · 3.39 Impact Factor
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    • "For example, does cytoplasmic ERK promote myogenic differentiation (or inhibits cell proliferation), and more specifically how does nuclear ERK suppress the differentiation of muscle progenitors? A plausible scenario for the effect of ERK on cell cycle progression, supported by the known functions of ERK in myogenesis (Knight and Kothary, 2011) and partially by our data (Figs 1, 2), is the following: activation of ERK and its translocation to the nucleus lead to the shuttling of p21 to Fig. 6 "
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