Article

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 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.

0 Followers
 · 
140 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The Cdo-p38MAPK signaling pathway plays important roles in regulating skeletal myogenesis. During myogenic differentiation, the cell surface receptor Cdo bridges scaffold proteins BNIP-2 and JLP and activates p38MAPK, but the spatial-temporal regulation of this process is largely unknown. We here report that KIF5B, the heavy chain of Kinesin-1 motor, is a novel interacting partner of BNIP-2. Coimmunoprecipitation and Far-Western study revealed that BNIP-2 directly interacted with the motor and tail domains of KIF5B via its BCH domain. By using a range of organelle markers and live microscopy, we determined the endosomal localization of BNIP-2 and revealed the microtubule-dependent anterograde transport of BNIP-2 in C2C12 cells. The anterograde transport of BNIP-2 was disrupted by a dominant negative mutant of KIF5B. In addition, knock-down of KIF5B causes aberrant aggregation of BNIP-2, confirming that KIF5B is critical for the anterograde transport BNIP-2 in cells. Gain- and loss-of-function experiments further showed that KIF5B modulates p38MAPK activity and in turn promotes myogenic differentiation. Importantly, the KIF5B-dependent anterograde transport of BNIP-2 is critical for its promyogenic effects. Our data reveal a novel role of KIF5B in the spatial regulation of Cdo-BNIP-2-p38MAPK signaling and disclosed a previously unappreciated linkage between the intracellular transporting system and myogenesis regulation.
    Molecular Biology of the Cell 11/2014; 26(1). DOI:10.1091/mbc.E14-03-0797 · 4.55 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: During skeletal muscle differentiation, the activation of some tissue-specific genes occurs immediately while others are delayed. The molecular basis controlling temporal gene regulation is poorly understood. We show that the regulatory sequences, but not other regions of genes expressed at late times of myogenesis, are in close physical proximity in differentiating embryonic tissue and in differentiating culture cells, despite these genes being located on different chromosomes. Formation of these inter-chromosomal interactions requires the lineage-determinant MyoD and functional Brg1, the ATPase subunit of SWI/SNF chromatin remodeling enzymes. Ectopic expression of myogenin and a specific Mef2 isoform induced myogenic differentiation without activating endogenous MyoD expression. Under these conditions, the regulatory sequences of late gene loci were not in close proximity, and these genes were prematurely activated. The data indicate that the spatial organization of late genes contributes to temporal regulation of myogenic transcription by restricting late gene expression during the early stages of myogenesis. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.
    Nucleic Acids Research 02/2015; 43(4). DOI:10.1093/nar/gkv046 · 8.81 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This study determined whether estradiol (E2) or the phytoestrogens genistein and daidzein regulate expression of growth-related and lipogenic genes in rainbow trout. Juvenile fish (5 mon, 65.8±1.8 g) received intraperitoneal injections of E2, genistein, or daidzein (5 μg/g body weight) or a higher dose of genistein (50 μg/g body weight). Liver and white muscle were harvested 24 hr post-injection. In liver, expression of vitellogenin (vtg) and estrogen receptor alpha (era1) increased in all treatments and reflected treatment estrogenicity (E2>genistein (50 μg/g)>genistein (5 μg/g)=daidzein (5 μg/g)). Estradiol and genistein (50 μg/g) reduced components of the growth hormone (GH)/insulin-like growth factor (IGF) axis in liver, including increased expression of IGF binding protein-2b1 (igfbp2b1) and reduced igfbp5b1. In liver E2 and genistein (50 μg/g) affected expression of components of the transforming growth factor beta signaling mechanism, reduced expression of ppar and rxr transcription factors, and increased expression of fatty acid synthesis genes srebp1, acly, fas, scd1, and gpat and lipid binding proteins fabp3 and lpl. In muscle E2 and genistein (50 μg/g) increased era1 and erb1 expression and decreased erb2 expression. Other genes responded to phytoestrogens in a manner that suggested regulation by estrogen receptor-independent mechanisms, including increased ghr2, igfbp2a, igfbp4, and igfbp5b1. Expression of muscle regulatory factors pax7 and myod were increased by E2 and genistein. These data indicate genistein and daidzein affect expression of genes in rainbow trout that regulate physiological mechanisms central to growth and nutrient retention. Published by Elsevier Inc.
    Comparative Biochemistry and Physiology Part C Toxicology & Pharmacology 02/2015; 170. DOI:10.1016/j.cbpc.2015.02.001 · 2.83 Impact Factor

Full-text (3 Sources)

Download
43 Downloads
Available from
Jun 1, 2014