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

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

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Researchpeer-review

15 Citations (Scopus)

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.
Original languageEnglish
Title of host publicationPhosphoinositides I: Enzymes of Synthesis and Degradation
EditorsT Balla, M Wymann, J D York
Place of PublicationUSA
PublisherSpringer
Pages281 - 336
Number of pages56
Edition1st
ISBN (Print)9789400730113
DOIs
Publication statusPublished - 2012

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