The hepatic PP1 glycogen-targeting subunit interaction with phosphorylase a can be blocked by C-terminal tyrosine deletion or an indole drug.
FEBS Lett
; 581(24): 4749-53, 2007 Oct 02.
Article
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| MEDLINE
| ID: mdl-17870073
ABSTRACT
The inhibition of hepatic glycogen-associated protein phosphatase-1 (PP1-G(L)) by glycogen phosphorylase a prevents the dephosphorylation and activation of glycogen synthase, suppressing glycogen synthesis when glycogenolysis is activated. Here, we show that a peptide ((280)LGPYY(284)) comprising the last five amino acids of G(L) retains high-affinity interaction with phosphorylase a and that the two tyrosines play crucial roles. Tyr284 deletion abolishes binding of phosphorylase a to G(L) and replacement by phenylalanine is insufficient to restore high-affinity binding. We show that a phosphorylase inhibitor blocks the interaction of phosphorylase a with the G(L) C-terminus, suggesting that the latter interaction could be targeted to develop an anti-diabetic drug.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fenilbutiratos
/
Tirosina
/
Glucógeno Fosforilasa de Forma Hepática
/
Indoles
Límite:
Animals
/
Humans
Idioma:
En
Revista:
FEBS Lett
Año:
2007
Tipo del documento:
Article
País de afiliación:
Reino Unido