The emerging interrelation between ROCO and related kinases, intracellular Ca2+ signaling, and autophagy.
Biochim Biophys Acta Mol Cell Res
; 1866(7): 1054-1067, 2019 07.
Article
em En
| MEDLINE
| ID: mdl-30582936
ABSTRACT
ROCO kinases form a family of proteins characterized by kinase activity in addition to the presence of the so-called ROC (Ras of complex proteins)/COR (C-terminal of ROC) domains having a role in their GTPase activity. These are the death-associated protein kinase (DAPK) 1 and the leucine-rich repeat kinases (LRRK) 1 and 2. These kinases all play roles in cellular life and death decisions and in autophagy in particular. Related to the ROCO kinases is DAPK 2 that however cannot be classified as a ROCO protein due to the absence of the ROC/COR domains. This review aims to bring together what is known about the relation between these proteins and intracellular Ca2+ signals in the induction and regulation of autophagy. Interestingly, DAPK 1 and 2 and LRRK2 are all linked to Ca2+ signaling in their effects on autophagy, though in various ways. Present evidence supports an upstream role for LRRK2 that via lysosomal and endoplasmic reticulum Ca2+ release can trigger autophagy induction. In contrast herewith, DAPK1 and 2 react on existing Ca2+ signals to stimulate the autophagic pathway. Further research will be needed for obtaining a full understanding of the role of these various kinases in autophagy and to assess their exact relation with intracellular Ca2+ signaling as this would be helpful in the development of novel therapeutic strategies against neurodegenerative disorders, cancer and auto-immune diseases. This article is part of a Special Issue entitled ECS Meeting edited by Claus Heizmann, Joachim Krebs and Jacques Haiech.
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MEDLINE
Assunto principal:
Autofagia
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Cálcio
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Proteínas Quinases Dependentes de Cálcio-Calmodulina
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Doenças Neurodegenerativas
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Sinalização do Cálcio
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Proteínas de Neoplasias
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Neoplasias
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article