Endosomal localization and receptor dynamics determine tyrosine phosphorylation of hepatocyte growth factor-regulated tyrosine kinase substrate.
Mol Cell Biol
; 20(20): 7685-92, 2000 Oct.
Article
en En
| MEDLINE
| ID: mdl-11003664
ABSTRACT
Hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) is a prominent substrate for activated tyrosine kinase receptors that has been proposed to play a role in endosomal membrane trafficking. The protein contains a FYVE domain, which specifically binds to the lipid phosphatidylinositol (PI) 3-phosphate (PI 3-P). We show that this interaction is required both for correct localization of the protein to endosomes that only partially coincides with early endosomal autoantigen 1 and for efficient tyrosine phosphorylation of the protein in response to epidermal growth factor stimulation. Treatment with wortmannin reveals that Hrs phosphorylation also requires PI 3-kinase activity, which is necessary to generate the PI 3-P required for localization. We have used both hypertonic media and expression of a dominant-negative form of dynamin (K44A) to inhibit endocytosis; under which conditions, receptor stimulation fails to elicit phosphorylation of Hrs. Our results provide a clear example of the coupling of a signal transduction pathway to endocytosis, from which we propose that activated receptor (or associated factor) must be delivered to the appropriate endocytic compartment in order for Hrs phosphorylation to occur.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Fosfoproteínas
/
Endosomas
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Receptores de Superficie Celular
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Fosfotirosina
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Cell Biol
Año:
2000
Tipo del documento:
Article
País de afiliación:
Reino Unido