Functional diversity of mammalian type 2C protein phosphatase isoforms: new tales from an old family.
1. The Type 2C protein phosphatases (PP2C) represent a highly conserved gene family in the mammalian genome. Recent studies have revealed that PP2C isoforms possess unique patterns of tissue and subcellular distribution associated with diverse functionalities. 2. The functional importance of PP2C isoforms has been shown in a plethora of signalling networks controlling cell differentiation, proliferation, growth, survival and metabolism. However, little is known about the regulatory mechanisms of PP2C at the molecular level. It is uncertain how PP2C isoforms are recruited, activated and inactivated during signalling transduction processes. 3. In the present paper, an overview of the critical functions of individual PP2C isoforms in regulating cellular signalling events will be provided, along with our perspectives on the challenging issues to be addressed. It is clear that a better understanding of the complex biological effects elicited by specific signalling pathways involving PP2C isoforms has great potential for developing novel therapies for a variety of human diseases, including cancer, diabetes and neural disorders, as well as cardiovascular diseases.
Lu
Gang
G
Department of Anaesthesiology, Molecular Biology Institute, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA.
Wang
Yibin
Y
D000818:Animals; D002453:Cell Cycle; D016923:Cell Death; D004249:DNA Damage; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008928:Mitochondria / Q000201:enzymology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D000071636:Protein Phosphatase 2C; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
D007527:Isoenzymes; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D010749:Phosphoprotein Phosphatases; D000071636:Protein Phosphatase 2C