Protein phosphatase 2C (PP2C) is one of the four major classes of mammalian serine/threonine specific protein phosphatases (3.1.3.16). PP2C [1] is a monomeric enzyme of about 42 kDa, that shows broad substrate specificity and is dependent on divalent cations (mainly manganese and magnesium) for its activity. The exact physiological role is still unclear. Three isozymes are currently known in mammals: PP2C-alpha, -beta and -gamma. In yeast, there are at least four PP2C homologues: phosphatase PTC1 [2] that have weak tyrosine phosphatase activity in addition to its activity on serines, phosphatases PTC2 and PTC3, and hypothetical protein YBR125c. Isozymes of PP2C are also known from Arabidopsis thaliana (Mouse-ear cress) (ABI1, PPH1), Caenorhabditis elegans (FEM-2, F42G9.1, T23F11.1), Leishmania chagasi and Paramecium tetraurelia. In A. thaliana, the kinase associated protein phosphatase (KAPP) [3] is an enzyme that dephosphorylates the Ser/Thr receptor-like kinase RLK5 and contains a C-terminal PP2C domain.

PP2C does not seem to be evolutionary related to the main family of serine/ threonine phosphatases: PP1, PP2A and PP2B. However, it is significantly similar to the catalytic subunit of pyruvate dehydrogenase phosphatase (3.1.3.43) (PDPC) [4], which catalyzes dephosphorylation and concomitant reactivation of the alpha subunit of the E1 component of the pyruvate dehydrogenase complex. PDPC is a mitochondrial enzyme and, like PP2C, is magnesium-dependent.

1. Molecular cloning and primary structure of a protein phosphatase 2C isoform. FEBS Lett. 297, 135-8
2. Mutations in a protein tyrosine phosphatase gene (PTP2) and a protein serine/threonine phosphatase gene (PTC1) cause a synthetic growth defect in Saccharomyces cerevisiae. Mol. Cell. Biol. 13, 5408-17
3. Interaction of a protein phosphatase with an Arabidopsis serine-threonine receptor kinase. Science 266, 793-5
4. Molecular cloning and expression of the catalytic subunit of bovine pyruvate dehydrogenase phosphatase and sequence similarity with protein phosphatase 2C. Biochemistry 32, 8987-93

Protein phosphatase 2C (PP2C) is one of the four major classes of mammalian serine/threonine spec
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