Inhibition of basal FGF receptor signaling by dimeric Grb2.
Cell
; 149(7): 1514-24, 2012 Jun 22.
Article
en En
| MEDLINE
| ID: mdl-22726438
ABSTRACT
Receptor tyrosine kinase activity is known to occur in the absence of extracellular stimuli. Importantly, this "background" level of receptor phosphorylation is insufficient to effect a downstream response, suggesting that strict controls are present and prohibit full activation. Here a mechanism is described in which control of FGFR2 activation is provided by the adaptor protein Grb2. Dimeric Grb2 binds to the C termini of two FGFR2 molecules. This heterotetramer is capable of a low-level receptor transphosphorylation, but C-terminal phosphorylation and recruitment of signaling proteins are sterically hindered. Upon stimulation, FGFR2 phosphorylates tyrosine residues on Grb2, promoting dissociation from the receptor and allowing full activation of downstream signaling. These observations establish a role for Grb2 as an active regulator of RTK signaling.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos
/
Proteína Adaptadora GRB2
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Cell
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos