Disease relevance of Ppm2c

• In the present study, recombinant rat protein phosphatase 2C (PrP-2C) expressed in Escherichia coli could dephosphorylate both Thr286/287 and Thr305/306 phosphorylation sites of CaM kinase II, which are responsible for the generation of Ca(2+)-independent activity and the inhibition of the total activity, respectively [1].
• These results suggest that concomitant greater PDK4 and less PDP1 expression in skeletal muscle of OLETF rats before the onset of diabetes are responsible for the lowering of the PDC activity and may be related with the development of diabetes mellitus [2].

High impact information on Ppm2c

• Protein phosphatase 2C binds selectively to and dephosphorylates metabotropic glutamate receptor 3 [3].
• Protein phosphatase 2C (PP2C), an Mg(2+)-dependent enzyme that dephosphorylates serine and threonine residues, defines one of the three major families of structurally unrelated eukaryotic protein phosphatases [4].
• Of the two PDP isoforms expressed in mammalian tissues, the Ca(2+)-sensitive isoform (PDP1) is highly expressed in rat heart, brain, and testis and is detectable but less abundant in rat muscle, lung, kidney, liver, and spleen [5].
• We describe the cloning of a cDNA encoding a novel neuronal protein, named NERPP-2C, which is distantly related to protein phosphatase 2C and plays a role in the inhibitory response pathway to myelin inhibitors [6].
• SCOP protein is predominantly expressed in the brain and has domains including a pleckstrin homology domain, leucine-rich repeats, a protein phosphatase 2C-like domain and a glutamine-rich region [7].

Biological context of Ppm2c

• A recently described 6-phosphofructo-1-kinase phosphatase (PFK-phosphatase) shared several properties with protein phosphatase 2C, but exhibited differences with respect to molecular mass and substrate specificity [8].

Anatomical context of Ppm2c

• The results with okadaic acid also suggest that protein phosphatase 2C is mainly responsible for dephosphorylation of the AMP-activated protein kinase in intact hepatocytes [9].
• Both compartments also had protein phosphatase 2B activity, whereas protein phosphatase 2C was only measurable in the plasma membrane fraction [10].

Associations of Ppm2c with chemical compounds

• Brain angiotensin-converting enzyme (PDP-1) cleaves Hip-His-Leu, but not 80 nM [3H-Tyr1, Leu5]-enkephalin, and is markedly inhibited by several specific inhibitors such as captopril, teprotide, and MK-422 [11].
• Both forms are markedly inactivated by incubation with the reactive ATP analogue p-fluorosulphonylbenzoyl adenosine (FSO2PhCOAdo), and also by mammalian protein phosphatase 2C, indicating that form B, like form A, is activated by phosphorylation [12].
• Palmitate increased phosphorylation of Thr172 within AMPK alpha-subunits and the activation by palmitate of both AMPK isoforms was abolished by protein phosphatase 2C leading to the conclusion that exposure to fatty acid caused activation of an AMPK kinase or inhibition of an AMPK phosphatase [13].
• Protein phosphatase 2C was the major enzyme acting on hydroxymethylglutaryl-CoA (HMG-CoA) reductase and HMG-CoA reductase kinase, suggesting an important role in the regulation of cholesterol synthesis [14].

Analytical, diagnostic and therapeutic context of Ppm2c

• The characteristics of the phosphatase, that is, 1) Mg2+ requirement for activity, 2) apparent molecular mass of 45 kDa by high performance liquid chromatography gel filtration, and 3) resistance to 100 microM okadaic acid, suggest that the primary phosphatase active in vitro is protein phosphatase 2C [15].
• Molecular cloning and primary structure of a protein phosphatase 2C isoform [16].

References