The structural requirements for ceramide activation of serine-threonine protein phosphatases

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The structural requirements for ceramide activation of serine-threonine protein phosphatases.

The protein phosphatases1 (PP1) and 2A (PP2A) serve as ceramide-activated protein phosphatases (CAPP). In this study, the structural requirements for interaction between ceramide and CAPP were determined. D-erythro-C(6) ceramide activated the catalytic subunit of PP2A (PP2Ac) approximately 3-fold in a stereospecific manner. In contrast, saturation of the 4-5 double bond, producing D-erythro-dih...

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Modulation of exocytosis is integral to the regulation of cellular signalling, and a variety of disorders (such as epilepsy, hypertension, diabetes and asthma) are closely associated with pathological modulation of exocytosis. Emerging evidence points to protein phosphatases as key regulators of exocytosis in many cells and, therefore, as potential targets for the design of novel therapies to t...

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The Structure and Topology of Protein Serine/Threonine Phosphatases

Structural studies of the two families of protein phosphatases responsible for dephosphorylating serine and threonine residues have revealed that, although these families are unrelated in sequence, the architecture of their catalytic domains is remarkably similar and distinct from the protein tyrosine phosphatases. The diversity of structure within the PPP and PPM families is generated by regul...

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Targeting protein serine/threonine phosphatases for drug development.

With the recent clinical success of drugs targeting protein kinase activity, drug discovery efforts are focusing on the role of reversible protein phosphorylation in disease states. The activity of protein phosphatases, enzymes that oppose protein kinases, can also be manipulated to alter cellular signaling for therapeutic benefits. In this review, we present protein serine/threonine phosphatas...

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ژورنال

عنوان ژورنال: Journal of Lipid Research

سال: 2004

ISSN: 0022-2275

DOI: 10.1194/jlr.m300347-jlr200