The Role of Ubiquitination and Hepatocyte Growth Factor-Regulated Tyrosine Kinase Substrate in the Degradation of the Adrenomedullin Type I Receptor.
Sci Rep
; 7(1): 12389, 2017 09 28.
Article
en En
| MEDLINE
| ID: mdl-28959041
ABSTRACT
Calcitonin receptor-like receptor (CLR) and the receptor activity-modifying protein 2 (RAMP2) comprise a receptor for adrenomedullin (AM). Although it is known that AM induces internalization of CLRâ¢RAMP2, little is known about the molecular mechanisms that regulate the trafficking of CLRâ¢RAMP2. Using HEK and HMEC-1 cells, we observed that AM-induced activation of CLRâ¢RAMP2 promoted ubiquitination of CLR. A mutant (CLRΔ9KR), lacking all intracellular lysine residues was functional and trafficked similar to the wild-type receptor, but was not ubiquitinated. Degradation of CLRâ¢RAMP2 and CLRΔ9KRâ¢RAMP2 was not dependent on the duration of AM stimulation or ubiquitination and occurred via a mechanism that was partially prevented by peptidase inhibitors. Degradation of CLRâ¢RAMP2 was sensitive to overexpression of hepatocyte growth factor-regulated tyrosine kinase substrate (HRS), but not to HRS knockdown, whereas CLRΔ9KRâ¢RAMP2 degradation was unaffected. Overexpression, but not knockdown of HRS, promoted hyperubiquitination of CLR under basal conditions. Thus, we propose a role for ubiquitin and HRS in the regulation of AM-induced degradation of CLRâ¢RAMP2.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Fosfoproteínas
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Adrenomedulina
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Ubiquitinación
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Complejos de Clasificación Endosomal Requeridos para el Transporte
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Receptores de Adrenomedulina
Límite:
Humans
Idioma:
En
Año:
2017
Tipo del documento:
Article