title: The PTEN and Myotubularin phosphoinositide 3-phosphatases: linking lipid signalling to human disease.
abstract: Two classes of lipid phosphatases selectively dephosphorylate the 3 position of the inositol ring of phosphoinositide signaling molecules: the PTEN and the Myotubularin families. PTEN dephosphorylates PtdIns(3,4,5)P(3), acting in direct opposition to the Class I PI3K enzymes in the regulation of cell growth, proliferation and polarity and is an important tumor suppressor. Although there are several PTEN-related proteins encoded by the human genome, none of these appear to fulfill the same functions. In contrast, the Myotubularins dephosphorylate both PtdIns(3)P and PtdIns(3,5)P(2), making them antagonists of the Class II and Class III PI 3-kinases and regulators of membrane traffic. Both phosphatase groups were originally identified through their causal mutation in human disease. Mutations in specific myotubularins result in myotubular myopathy and Charcot-Marie-Tooth peripheral neuropathy; and loss of PTEN function through mutation and other mechanisms is evident in as many as a third of all human tumors. This chapter will discuss these two classes of phosphatases, covering what is known about their biochemistry, their functions at the cellular and whole body level and their influence on human health.
authors.affiliation: Division of Cell Signalling and Immunology, Wellcome Trust Biocentre, College of Life Sciences, University of Dundee, Dow Street, DD1 5EH, Dundee, Scotland, United Kingdom, n.r.leslie@dundee.ac.uk.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Davies
authors.forename: David A
authors.initials: DA
authors.lastname: Sheffield
authors.forename: Priyanka
authors.initials: P
authors.lastname: Tibarewal
authors.forename: Clare G
authors.initials: CG
authors.lastname: Fedele
authors.forename: Christina A
authors.initials: CA
authors.lastname: Mitchell
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Leslie
mesh_terms: D002607:Charcot-Marie-Tooth Disease / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D006868:Hydrolysis; D009154:Mutation; D020914:Myopathies, Structural, Congenital / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010766:Phosphorylation; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000235:genetics / Q000378:metabolism*; D015290:Second Messenger Systems; D013379:Substrate Specificity
chemical_list: D018129:Phosphatidylinositol Phosphates; C060974:phosphatidylinositol 3,4,5-triphosphate; C106336:phosphatidylinositol 3,5-diphosphate; C055525:phosphatidylinositol 3-phosphate; D019869:Phosphatidylinositol 3-Kinases; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C099588:myotubularin; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human