Author, as appears in the article.: Garcia-Guerra, Lucia; Vila-Bedmar, Rocio; Carrasco-Rando, Marta; Cruces-Sande, Marta; Martin, Mercedes; Ruiz-Gomez, Ana; Ruiz-Gomez, Mar; Lorenzo, Margarita; Fernandez-Veledo, Sonia; Mayor, Federico, Jr.; Murga, Cristina; Nieto-Vazquez, Iria;
Department: Ciències Mèdiques Bàsiques
URV's Author/s: Fernandez Veledo, Sonia
Keywords: akt grk2 myogenesis p38mapk Akt C2c12 myoblasts Cell-cycle withdrawal Drosophila Flight muscles Gene-expression Grk2 Kappa-b Myoblast differentiation Myogenesis P38 map kinase P38mapk Pathway Phosphatidylinositol 3-kinase Skeletal muscle
Abstract: 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.
Thematic Areas: Cell biology Genetics Medicine (all) Medicine (miscellaneous) Molecular biology
licence for use: https://creativecommons.org/licenses/by/3.0/es/
Author's mail: sonia.fernandez@urv.cat
Author identifier: 0000-0003-2906-3788
Record's date: 2023-05-20
Papper version: info:eu-repo/semantics/acceptedVersion
Link to the original source: https://academic.oup.com/jmcb/article/6/4/299/2886284?login=false
Papper original source: Journal Of Molecular Cell Biology. 6 (4): 299-311
APA: Garcia-Guerra, Lucia; Vila-Bedmar, Rocio; Carrasco-Rando, Marta; Cruces-Sande, Marta; Martin, Mercedes; Ruiz-Gomez, Ana; Ruiz-Gomez, Mar; Lorenzo, Mar (2014). Skeletal muscle myogenesis is regulated by G protein-coupled receptor kinase 2. Journal Of Molecular Cell Biology, 6(4), 299-311. DOI: 10.1093/jmcb/mju025
Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/
Article's DOI: 10.1093/jmcb/mju025
Entity: Universitat Rovira i Virgili
Journal publication year: 2014
Publication Type: Journal Publications
Repositori URV