N-Myristoylation is essential for protein phosphatases PPM1A and PPM1B to dephosphorylate their physiological substrates in cells

Biochemical Journal (Impact Factor: 4.78). 10/2012; 449(3). DOI: 10.1042/BJ20121201
Source: PubMed

ABSTRACT Metal-dependent protein phosphatase (PPM, formerly called PP2C) family members play essential roles in regulating a variety of signaling pathways. While searching for protein phosphatase(s) that act on AMP-activated protein kinase (AMPK), we found that PPM1A and PPM1B are N-myristoylated and that this modification is essential for their ability to dephosphorylate the a subunit of AMPK (AMPKa) in cells. N-myristoylation was also required for two other functions of PPM1A and PPM1B in cells. Although a non-myristoylated mutation (G2A) of PPM1A and PPM1B prevented membrane association, this relocalization did not likely cause the decreased activity toward AMPKa. In in vitro experiments, the G2A mutants exhibited reduced activities toward AMPKa but much higher specific activity against an artificial substrate, pNPP, compared to the wild-type counterparts. Taken together, these observations suggest that N-myristoylation of PPM1A and PPM1B plays a key role in recognition of their physiological substrates in cells.

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    • "Lipid modifications of proteins play many roles inside and outside the cell [4]. They facilitate membrane attachment of soluble proteins by enhancing interactions of proteins with either organelle or plasma membranes, occur in signaling and subcellular targeting by directing proteins to various cellular membranes, promote intra-and intermolecular protein–protein interactions, and may modulate protein structure and function [5] [6] [7] [8] [9] [10]. "
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