The PTEN and Myotubularin phosphoinositide 3-phosphatases: linking lipid signalling to human disease

Elizabeth M. Davies, David A. Sheffield, Priyanka Tibarewal, Clare G. Fedele, Christina A. Mitchell, Nicholas R. Leslie

    Research output: Chapter in Book/Report/Conference proceedingChapter

    18 Citations (Scopus)


    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)P3, 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)P2, 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.

    Original languageEnglish
    Title of host publicationPhosphoinositides I
    Subtitle of host publicationenzymes of synthesis and degradation
    EditorsTamas Balla, Matthias Wymann, John D. York
    Place of PublicationDordrecht, Netherlands
    PublisherSpringer Netherlands
    Number of pages56
    ISBN (Print)9789400730113
    Publication statusPublished - 2012

    Publication series

    NameSubcellular Biochemistry
    PublisherSpringer Netherlands
    ISSN (Print)0306-0225


    • Charcot-Marie-Tooth Disease
    • Gene Expression Regulation
    • Humans
    • Hydrolysis
    • Mutation
    • Myopathies, Structural, Congenital
    • PTEN Phosphohydrolase
    • Phosphatidylinositol 3-Kinases
    • Phosphatidylinositol Phosphates
    • Phosphorylation
    • Protein Tyrosine Phosphatases, Non-Receptor
    • Second Messenger Systems
    • Substrate Specificity


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