Biochemical and functional characterization of the ROC domain of DAPK establishes a new paradigm of GTP regulation in ROCO proteins.
Biochem Soc Trans
; 40(5): 1052-7, 2012 Oct.
Article
em En
| MEDLINE
| ID: mdl-22988864
DAPK (death-associated protein kinase) is a newly recognized member of the mammalian family of ROCO proteins, characterized by common ROC (Ras of complex proteins) and COR (C-terminal of ROC) domains. In the present paper, we review our recent work showing that DAPK is functionally a ROCO protein; its ROC domain binds and hydrolyses GTP. Furthermore, GTP binding regulates DAPK catalytic activity in a novel manner by enhancing autophosphorylation on inhibitory Ser308, thereby promoting the kinase 'off' state. This is a novel mechanism for in cis regulation of kinase activity by the distal ROC domain. The functional similarities between DAPK and the Parkinson's disease-associated protein LRRK2 (leucine-rich repeat protein kinase 2), another member of the ROCO family, are also discussed.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Quinases Dependentes de Cálcio-Calmodulina
/
Proteínas Reguladoras de Apoptose
/
Guanosina Trifosfato
Limite:
Humans
Idioma:
En
Revista:
Biochem Soc Trans
Ano de publicação:
2012
Tipo de documento:
Article
País de publicação:
Reino Unido