Phosphatase Gene PPM1E

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Phosphatase Classification: Superfamily PPM (PP2C): Family PPM (PP2C): Subfamily PPM1E: Gene PPM1E

PPM1E (also known as POXP1, PP2CH, caMKN, CaMKP-N).

PPM1E and another phosphatase of this subfamily PPM1F (also known as POXP2, CAMKP, FEM-2, hFEM-2, CaMKPase) dephosphorylate and regulate multifunctional Ca(2+)/calmodulin-dependent protein kinases (CaMKs). PPM1E dephosphorylates CaMKIV and nuclear CaMKII, whereas PPM1F dephosphorylates CaMKI and cytosolic CaMKII. their localizations are different [1]. PPM1E is localized in the nucleus, whereas PPM1F is localized in the cytosol. PPM1E contains two NLSs, NLS1 and NLS2, at the C-terminus. A cluster of basic residues in the NLSs is important for their function. NLS1 and NLS2 function independently, but mutagenesis analysis suggests that these NLSs interact with each other [2].

PPM1E and PPM1F also dephoshorylate p21 (Cdc42/Rac)- activated kinase PAK [3].

PPM1E and PPM1F also dephosphorylate 5'-AMP-activated protein kinase (AMPK) [4]. The activation of AMPK is related to the treatment of type 2 diabetes.

References

  1. Takeuchi M, Ishida A, Kameshita I, Kitani T, Okuno S, and Fujisawa H. Identification and characterization of CaMKP-N, nuclear calmodulin-dependent protein kinase phosphatase. J Biochem. 2001 Dec;130(6):833-40. DOI:10.1093/oxfordjournals.jbchem.a003055 | PubMed ID:11726284 | HubMed [Takeuchi01]
  2. Takeuchi M, Taniguchi T, and Fujisawa H. Identification and characterization of nuclear localization signals of CaMKP-N. J Biochem. 2004 Aug;136(2):183-8. DOI:10.1093/jb/mvh109 | PubMed ID:15496589 | HubMed [Takeuchi04]
  3. Koh CG, Tan EJ, Manser E, and Lim L. The p21-activated kinase PAK is negatively regulated by POPX1 and POPX2, a pair of serine/threonine phosphatases of the PP2C family. Curr Biol. 2002 Feb 19;12(4):317-21. DOI:10.1016/s0960-9822(02)00652-8 | PubMed ID:11864573 | HubMed [Koh02]
  4. Voss M, Paterson J, Kelsall IR, Martín-Granados C, Hastie CJ, Peggie MW, and Cohen PT. Ppm1E is an in cellulo AMP-activated protein kinase phosphatase. Cell Signal. 2011 Jan;23(1):114-24. DOI:10.1016/j.cellsig.2010.08.010 | PubMed ID:20801214 | HubMed [Voss12]
All Medline abstracts: PubMed | HubMed