Vav2 catalysis-dependent pathways contribute to skeletal muscle growth and metabolic homeostasis.

[EN]Skeletal muscle promotes metabolic balance by regulating glucose uptake and the stimulation of multiple interorgan crosstalk. We show here that the catalytic activity of Vav2, a Rho GTPase activator, modulates the signaling output of the IGF1- and insulin-stimulated phosphatidylinositol 3-kinase...

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Detalles Bibliográficos
Autores: Rodríguez-Fdez, Sonia, Lorenzo Martín, Luis Francisco, Fernández-Pisonero, Isabel, Porteiro, Begoña, Veyrat-Durebex, Christelle, Beiroa, Daniel, Al-Massadi, Omar, Abad, Antonio, Diéguez, Carlos, Coppari, Roberto, Nogueiras, Rubén, Bustelo, Xosé R.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Universidad de Salamanca (USAL)
Repositorio:GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:oai:gredos.usal.es:10366/166940
Acceso en línea:http://hdl.handle.net/10366/166940
Access Level:acceso abierto
Palabra clave:Skeletal muscle
Rho GTPase activator
Insulin responsiveness
Proto-Oncogene Proteins c-vav
Muscle Cells
Metabolism
Body Composition
Signal Transduction
Adipocytes
Adipose Tissue
Mice
transducción de señales
adipocitos
ratones
proteínas protooncogénicas c-vav
células musculares
tejido adiposo
composición corporal
metabolismo
Descripción
Sumario:[EN]Skeletal muscle promotes metabolic balance by regulating glucose uptake and the stimulation of multiple interorgan crosstalk. We show here that the catalytic activity of Vav2, a Rho GTPase activator, modulates the signaling output of the IGF1- and insulin-stimulated phosphatidylinositol 3-kinase pathway in that tissue. Consistent with this, mice bearing a Vav2 protein with decreased catalytic activity exhibit reduced muscle mass, lack of proper insulin responsiveness and, at much later times, a metabolic syndrome-like condition. Conversely, mice expressing a catalytically hyperactive Vav2 develop muscle hypertrophy and increased insulin responsiveness. Of note, while hypoactive Vav2 predisposes to, hyperactive Vav2 protects against high fat diet-induced metabolic imbalance. These data unveil a regulatory layer affecting the signaling output of insulin family factors in muscle.