Articles producció científica> Ciències Mèdiques Bàsiques

Skeletal muscle myogenesis is regulated by G protein-coupled receptor kinase 2

  • Identification data

    Identifier: imarina:9298964
    Authors:
    Garcia-Guerra, LuciaVila-Bedmar, RocioCarrasco-Rando, MartaCruces-Sande, MartaMartin, MercedesRuiz-Gomez, AnaRuiz-Gomez, MarLorenzo, MargaritaFernandez-Veledo, SoniaMayor, Federico, Jr.Murga, CristinaNieto-Vazquez, Iria
    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.
  • Others:

    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: Skeletal muscle Phosphatidylinositol 3-kinase Pathway P38mapk P38 map kinase Myogenesis Myoblast differentiation Kappa-b Grk2 Gene-expression Flight muscles Drosophila Cell-cycle withdrawal C2c12 myoblasts Akt p38mapk myogenesis grk2 akt
    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: Molecular biology Medicine (miscellaneous) Medicine (all) Genetics Cell 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: 2024-09-07
    Papper version: info:eu-repo/semantics/acceptedVersion
    Link to the original source: https://academic.oup.com/jmcb/article/6/4/299/2886284?login=false
    Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
    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
    Article's DOI: 10.1093/jmcb/mju025
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2014
    Publication Type: Journal Publications
  • Keywords:

    Cell Biology,Genetics,Medicine (Miscellaneous),Molecular Biology
    Skeletal muscle
    Phosphatidylinositol 3-kinase
    Pathway
    P38mapk
    P38 map kinase
    Myogenesis
    Myoblast differentiation
    Kappa-b
    Grk2
    Gene-expression
    Flight muscles
    Drosophila
    Cell-cycle withdrawal
    C2c12 myoblasts
    Akt
    p38mapk
    myogenesis
    grk2
    akt
    Molecular biology
    Medicine (miscellaneous)
    Medicine (all)
    Genetics
    Cell biology
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