Skeletal muscle myogenesis is regulated by G protein-coupled receptor kinase 2
Entity
UAM. Departamento de Biología MolecularPublisher
Oxford University PressDate
2014-01-01Citation
10.1093/jmcb/mju025
Journal of Molecular Cell Biology 6.4 (2014): 299-311
ISSN
1674-2788 (print); 1759-4685 (online)DOI
10.1093/jmcb/mju025Funded by
This work was supported by Grants BFU2008-04043 (to M.L. and S.F.-V.), SAF2012-3618 (to S.F.-V.), and SAF2011-23800 (to F.M.) from Ministerio de Economía y Competitividad, Spain; S2010/BMD-2332 (INDISNET) from Comunidad de Madrid, Spain (to F.M.); CIBER de Diabetes y Enfermedades Metabólicas Asociadas and The Cardiovascular Network (RD06- 0014/0037 and RD12/0042/0012) from Ministerio Sanidad y Consumo-Instituto Carlos III, Spain (to F.M.); UAM-Banco de Santander (to C.M.); BFU2010-14884 (to M.R.-G.). S.F.-V. is recipient of a ‘Miguel Servet’ tenure track program (CP10/00438) co-financed by the European Regional Development Fund (ERDF). We also acknowledge the support of COST Action BM0602 from the European Commission (to M.L.) and institutional support from Fundación Ramón ArecesProject
Comunidad de Madrid. S2010/BMD-2332/INDISNETEditor's Version
http://dx.doi.org/10.1093/jmcb/mju025Subjects
Akt; GRK2; myogenesis; p38MAPK; skeletal muscle; Biología y Biomedicina / BiologíaNote
This is a pre-copyedited, author-produced pdf of an article accepted for publication in Journal of Molecular Cell Biology following peer review. The version of record Journal of Molecular Cell Biology 6.4 (2014) is available online at: http://dx.doi.org/10.1093/jmcb/mju025Rights
© The Author 2014Abstract
G protein-coupled receptor kinase 2 (GRK2) is an important serine/threonine-kinase regulating
different membrane receptors and intracellular proteins. Attenuation of Drosophila Gprk2 in
embryos or adult flies induced a defective differentiation of somatic muscles, loss of fibers, and
a flightless phenotype. In vertebrates, GRK2 hemizygous mice contained less but more
hypertrophied skeletal muscle fibers than wild-type littermates. In C2C12 myoblasts
overexpression of a GRK2 kinase-deficient mutant (K220R) caused precocious differentiation
of cells into immature myotubes, which were wider in size and contained more fused nuclei,
while GRK2 overexpression blunted differentiation. Moreover, p38MAPK and Akt pathways
were activated at an earlier stage and to a greater extent in K220R-expressing cells or upon
kinase downregulation, while the activation of both kinases was impaired in GRK2-
overexpressing cells. The impaired differentiation and fewer fusion events promoted by
enhanced GRK2 levels were recapitulated by a p38MAPK mutant, which was able to mimic the
inhibitory phosphorylation of p38MAPK by GRK2, whereas the blunted differentiation
observed in GRK2-expressing clones was rescued in the presence of a constitutively active
upstream stimulator of the p38MAPK pathway. These results suggest that balanced GRK2
function is necessary for a timely and complete myogenic process.
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Google Scholar:Garcia-Guerra, Lucia
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Vila Bedmar, Rocío
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Carrasco-Rando, Marta
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Cruces-Sande, Marta
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Martín, Mercedes
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Ruiz Gómez, Ana
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Lorenzo, Margarita
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Fernández-Veledo, Sonia
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Mayor Menéndez, Federico
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Murga Montesinos, Cristina
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Nieto-Vázquez, Iria
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