Protein phosphatase

From Proteopedia

Contents 1 Function 2 Disease 3 Structural highlights 4 3D Structures of protein phosphatase Function Protein phosphatases (PP) or serine/threonine protein phosphatase regulate protein phosphorylation and thus are key in intracellular signal transduction processes. PP1 is a serine/threonine phosphatase and is a key component of the insulin signaling pathway[1]. PP1C is the catalytic subunit of PP1. PP1K is Mn+2/Mg+2-dependent PP1. PP2A targets proteins in the oncogenic signaling pathways[2]. For PP2A see also HEAT Repeat. PP2C are Mg/Mn-dependent and are essential for the regulation of cell cycle and stress signaling pathways. For details see PP2Cm Protein Phosphatase 2C ABA-regulated Protein Phosphatase 2C ABA Signaling Pathway. PP4 regulates a variety of cellular functions[3]. PP5 is activated by lipids and is involved in signal transduction[4]. Disease Mutations in PP2A are found in many solid cancers and leukemias. PP2A-activating drugs are possible candidates for cancer therapeutics protocols[5]. Development of Alzheimer disease drugs could be based on restoration of PP2A activity[6]. Structural highlights Human PP2A catalytic (green) and regulatory (cyan) subunits complex with tumor-inducing toxin. Algal toxin binds at the surface pocket of the PP2A catalytic subunit which contains the Mn+2 ion cofactors[7]. Water molecule are shown as red sphere. Mn+2 ion cofactors coordination site. Whole binding site. 3D Structures of protein phosphatase Protein phosphatase 3D structures

spinqualitylabelsall models Human PP2A catalytic (green) and regulatory (cyan) subunits complex with tumor-inducing toxin and sulfate 3k7v Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

References

1. ↑ Ragolia L, Begum N. Protein phosphatase-1 and insulin action. Mol Cell Biochem. 1998 May;182(1-2):49-58. PMID:9609113
2. ↑ Resjo S, Goransson O, Harndahl L, Zolnierowicz S, Manganiello V, Degerman E. Protein phosphatase 2A is the main phosphatase involved in the regulation of protein kinase B in rat adipocytes. Cell Signal. 2002 Mar;14(3):231-8. PMID:11812651
3. ↑ Lipinszki Z, Lefevre S, Savoian MS, Singleton MR, Glover DM, Przewloka MR. Centromeric binding and activity of Protein Phosphatase 4. Nat Commun. 2015 Jan 6;6:5894. doi: 10.1038/ncomms6894. PMID:25562660 doi:http://dx.doi.org/10.1038/ncomms6894
4. ↑ Chinkers M. Protein phosphatase 5 in signal transduction. Trends Endocrinol Metab. 2001 Jan-Feb;12(1):28-32. PMID:11137038
5. ↑ Perrotti D, Neviani P. Protein phosphatase 2A: a target for anticancer therapy. Lancet Oncol. 2013 May;14(6):e229-38. doi: 10.1016/S1470-2045(12)70558-2. PMID:23639323 doi:http://dx.doi.org/10.1016/S1470-2045(12)70558-2
6. ↑ Rudrabhatla P, Pant HC. Role of protein phosphatase 2A in Alzheimer's disease. Curr Alzheimer Res. 2011 Sep;8(6):623-32. PMID:21605044
7. ↑ Huhn J, Jeffrey PD, Larsen K, Rundberget T, Rise F, Cox NR, Arcus V, Shi Y, Miles CO. A structural basis for the reduced toxicity of dinophysistoxin-2. Chem Res Toxicol. 2009 Nov;22(11):1782-6. PMID:19916524 doi:10.1021/tx9001622