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

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Citation

Chida T, Ando M, Matsuki T, Masu Y, Nagaura Y, Takano-Yamamoto T, Tamura S, Kobayashi T

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

Biochem J. 2013 Feb 1;449(3):741-9. doi: 10.1042/BJ20121201.

PubMed ID
23088624 [ View in PubMed
]
Abstract

PPM [metal-dependent protein phosphatase, formerly called PP2C (protein phosphatase 2C)] family members play essential roles in regulating a variety of signalling pathways. While searching for protein phosphatase(s) that act on AMPK (AMP-activated protein kinase), we found that PPM1A and PPM1B are N-myristoylated and that this modification is essential for their ability to dephosphorylate the alpha subunit of AMPK (AMPKalpha) 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 towards AMPKalpha. In in vitro experiments, the G2A mutants exhibited reduced activities towards AMPKalpha, but much higher specific activity against an artificial substrate, PNPP (p-nitrophenyl phosphate), compared with the wild-type counterparts. Taken together, the results of the present study suggest that N-myristoylation of PPM1A and PPM1B plays a key role in recognition of their physiological substrates in cells.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
5'-AMP-activated protein kinase catalytic subunit alpha-1Q13131Details
5'-AMP-activated protein kinase catalytic subunit alpha-2P54646Details