Protein phosphatase
From Proteopedia
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{{STRUCTURE_3k7v| PDB=3k7v | SIZE=400| SCENE= |right|CAPTION=Human PP2A catalytic (pink) and regulatory (grey) subunits complex with tumor-inducing toxin and sulfate [[3k7v]] }} | {{STRUCTURE_3k7v| PDB=3k7v | SIZE=400| SCENE= |right|CAPTION=Human PP2A catalytic (pink) and regulatory (grey) subunits complex with tumor-inducing toxin and sulfate [[3k7v]] }} | ||
| - | '''Protein phosphatases''' (PP) | + | '''Protein phosphatases''' (PP) regulate protein phosphorylation and thus are key in intracellular signal transduction processes.<br /> |
* '''PP1''' is a serine/threonine phosphatase and is a key component of the insulin signaling pathway<ref>PMID:9609113</ref>.<br /> | * '''PP1''' is a serine/threonine phosphatase and is a key component of the insulin signaling pathway<ref>PMID:9609113</ref>.<br /> | ||
* '''PP2A''' targets proteins in the oncogenic signaling pathways<ref>PMID:11812651</ref>. For PP2A see also [[HEAT Repeat]].<br /> | * '''PP2A''' targets proteins in the oncogenic signaling pathways<ref>PMID:11812651</ref>. For PP2A see also [[HEAT Repeat]].<br /> | ||
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== Disease == | == Disease == | ||
Mutations in PP2A are found in many solid cancers and leukemias. PP2A-activating drugs are possible candidates for cancer therapeutics protocols<ref>PMID:23639323</ref>. Development of Alzheimer disease drugs could be based on restoration of PP2A activity<ref>PMID:21605044</ref>. | Mutations in PP2A are found in many solid cancers and leukemias. PP2A-activating drugs are possible candidates for cancer therapeutics protocols<ref>PMID:23639323</ref>. Development of Alzheimer disease drugs could be based on restoration of PP2A activity<ref>PMID:21605044</ref>. | ||
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| + | == Structural highlights == | ||
| + | Algal toxin binds at the surface pocket of the PP2A catalytic subunit which contains the Mn+2 ion cofactors<ref>PMID:19916524</ref>. | ||
== 3D Structures of protein phosphatase== | == 3D Structures of protein phosphatase== | ||
Revision as of 09:46, 18 July 2016
Protein phosphatases (PP) 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].
- 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 ABA-regulated Protein Phosphatase 2C.
- PP4 regulates a variety of cellular functions[3].
- PP5 is activated by lipids and is involved in signal transduction[4].
Contents |
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
Algal toxin binds at the surface pocket of the PP2A catalytic subunit which contains the Mn+2 ion cofactors[7].
3D Structures of protein phosphatase
Updated on 18-July-2016
References
- ↑ Ragolia L, Begum N. Protein phosphatase-1 and insulin action. Mol Cell Biochem. 1998 May;182(1-2):49-58. PMID:9609113
- ↑ 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
- ↑ 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
- ↑ Chinkers M. Protein phosphatase 5 in signal transduction. Trends Endocrinol Metab. 2001 Jan-Feb;12(1):28-32. PMID:11137038
- ↑ 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
- ↑ Rudrabhatla P, Pant HC. Role of protein phosphatase 2A in Alzheimer's disease. Curr Alzheimer Res. 2011 Sep;8(6):623-32. PMID:21605044
- ↑ 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
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