Protein kinase inhibitor ß enhances the constitutive activity of G-protein-coupled zinc receptor GPR39.
Biochem J
; 462(1): 125-32, 2014 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-24869658
ABSTRACT
GPR39 is a G-protein-coupled zinc receptor that protects against diverse effectors of cell death. Its protective activity is mediated via constitutive activation of Gα13 and the RhoA pathway, leading to increased SRE (serum-response element)-dependent transcription; the zinc-dependent immediate activation of GPR39 involves Gq-mediated increases in cytosolic Ca2+ and Gs coupling leading to increased cAMP levels. We used the cytosolic and soluble C-terminus of GPR39 in a Y2H (yeast-2-hybrid) screen for interacting proteins, thus identifying PKIB (protein kinase A inhibitor ß). Co-expression of GPR39 with PKIB increased the protective activity of GPR39 via the constitutive, but not the ligand-mediated, pathway. PKIB inhibits protein kinase A by direct interaction with its pseudosubstrate domain; mutation of this domain abolished the inhibitory activity of PKIB on protein kinase A activity, but had no effect on the interaction with GPR39, cell protection and induction of SRE-dependent transcription. Zinc caused dissociation of PKIB from GPR39, thereby liberating it to associate with protein kinase A and inhibit its activity, which would result in a negative-feedback loop with the ability to limit activation of the Gs pathway by zinc.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores Acoplados a Proteínas G
/
Peptídeos e Proteínas de Sinalização Intracelular
/
Inibidores de Proteínas Quinases
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Biochem J
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Alemanha