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

doi:10.1007/978-94-007-3012-0_8

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 proceeding › Chapter

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)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 language	English
Title of host publication	Phosphoinositides I
Subtitle of host publication	enzymes of synthesis and degradation
Editors	Tamas Balla, Matthias Wymann, John D. York
Place of Publication	Dordrecht, Netherlands
Publisher	Springer Netherlands
Pages	281-336
Number of pages	56
Volume	58
ISBN (Print)	9789400730113
DOIs	https://doi.org/10.1007/978-94-007-3012-0_8
Publication status	Published - 2012

Publication series

Name	Subcellular Biochemistry
Publisher	Springer Netherlands
Volume	58
ISSN (Print)	0306-0225

Keywords

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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Davies, E. M., Sheffield, D. A., Tibarewal, P., Fedele, C. G., Mitchell, C. A., & Leslie, N. R. (2012). The PTEN and Myotubularin phosphoinositide 3-phosphatases: linking lipid signalling to human disease. In T. Balla, M. Wymann, & J. D. York (Eds.), Phosphoinositides I: enzymes of synthesis and degradation (Vol. 58, pp. 281-336). (Subcellular Biochemistry ; Vol. 58). Springer Netherlands. https://doi.org/10.1007/978-94-007-3012-0_8

Davies, Elizabeth M. ; Sheffield, David A. ; Tibarewal, Priyanka ; Fedele, Clare G. ; Mitchell, Christina A. ; Leslie, Nicholas R. / The PTEN and Myotubularin phosphoinositide 3-phosphatases : linking lipid signalling to human disease. Phosphoinositides I: enzymes of synthesis and degradation . editor / Tamas Balla ; Matthias Wymann ; John D. York. Vol. 58 Dordrecht, Netherlands : Springer Netherlands, 2012. pp. 281-336 (Subcellular Biochemistry ).

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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)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.",

keywords = "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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Davies, EM, Sheffield, DA, Tibarewal, P, Fedele, CG, Mitchell, CA & Leslie, NR 2012, The PTEN and Myotubularin phosphoinositide 3-phosphatases: linking lipid signalling to human disease. in T Balla, M Wymann & JD York (eds), Phosphoinositides I: enzymes of synthesis and degradation . vol. 58, Subcellular Biochemistry , vol. 58, Springer Netherlands, Dordrecht, Netherlands, pp. 281-336. https://doi.org/10.1007/978-94-007-3012-0_8

The PTEN and Myotubularin phosphoinositide 3-phosphatases : linking lipid signalling to human disease. / Davies, Elizabeth M.; Sheffield, David A.; Tibarewal, Priyanka; Fedele, Clare G.; Mitchell, Christina A.; Leslie, Nicholas R.

Phosphoinositides I: enzymes of synthesis and degradation . ed. / Tamas Balla; Matthias Wymann; John D. York. Vol. 58 Dordrecht, Netherlands : Springer Netherlands, 2012. p. 281-336 (Subcellular Biochemistry ; Vol. 58).

Research output: Chapter in Book/Report/Conference proceeding › Chapter

TY - CHAP

T1 - The PTEN and Myotubularin phosphoinositide 3-phosphatases

T2 - linking lipid signalling to human disease

AU - Davies, Elizabeth M.

AU - Sheffield, David A.

AU - Tibarewal, Priyanka

AU - Fedele, Clare G.

AU - Mitchell, Christina A.

AU - Leslie, Nicholas R.

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

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KW - Mutation

KW - Myopathies, Structural, Congenital

KW - PTEN Phosphohydrolase

KW - Phosphatidylinositol 3-Kinases

KW - Phosphatidylinositol Phosphates

KW - Phosphorylation

KW - Protein Tyrosine Phosphatases, Non-Receptor

KW - Second Messenger Systems

KW - Substrate Specificity

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DO - 10.1007/978-94-007-3012-0_8

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Davies EM, Sheffield DA, Tibarewal P, Fedele CG, Mitchell CA, Leslie NR. The PTEN and Myotubularin phosphoinositide 3-phosphatases: linking lipid signalling to human disease. In Balla T, Wymann M, York JD, editors, Phosphoinositides I: enzymes of synthesis and degradation . Vol. 58. Dordrecht, Netherlands: Springer Netherlands. 2012. p. 281-336. (Subcellular Biochemistry ). https://doi.org/10.1007/978-94-007-3012-0_8