English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/169369
COMPARTIR / IMPACTO:
Estadísticas
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:
Título

New insights into the Vav1 activation cycle in lymphocytes

AutorBarreira, María; Rodríguez-Fdez, Sonia; Bustelo, Xosé R.
Palabras claveB cell receptor
Phosphosites
Conformational states
Signaling diversification
Lymphocytes
Zap70
Src family
Lck
NFAT
JNK
Rac1
Exchange factors
T cell receptor
Protein tyrosine phosphatases
Lat
Phospholipase Cγ
Slp76
Fecha de publicación2018
EditorElsevier
CitaciónCellular Signalling 45: 132-144 (2018)
ResumenVav1 is a hematopoietic-specific Rho GDP/GTP exchange factor and signaling adaptor. Although these activities are known to be stimulated by direct Vav1 phosphorylation, little information still exists regarding the regulatory layers that influence the overall Vav1 activation cycle. Using a collection of cell models and activation-mimetic Vav1 mutants, we show here that the dephosphorylated state of Vav1 in nonstimulated T cells requires the presence of a noncatalytic, phospholipase Cγ1–Slp76-mediated inhibitory pathway. Upon T cell stimulation, Vav1 becomes rapidly phosphorylated via the engagement of Lck and, to a much lesser extent, other Src family kinases and Zap70. In this process, Lck, Zap70 and the adaptor protein Lat contribute differently to the dynamics and amplitude of the Vav1 phosphorylated pool. Consistent with a multiphosphosite activation mechanism, the optimal stimulation of Vav1 can only be recapitulated by the combination of several activation-mimetic phosphosite mutants. The analysis of these mutants has also unveiled the presence of different Vav1 signaling competent states that are influenced by phosphosites present in the N- and C-terminal domains of the protein.
URIhttp://hdl.handle.net/10261/169369
Identificadoresdoi: 10.1016/j.cellsig.2018.01.026
e-issn: 1873-3913
issn: 0898-6568
Aparece en las colecciones: (IBMCC) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
accesoRestringido.pdf15,38 kBAdobe PDFVista previa
Visualizar/Abrir
Mostrar el registro completo
 

Artículos relacionados:


NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.