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

18 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

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

Aref#d: 21320. Antagonism of PI 3-Kinase Signalling by PTEN and SHIP2 (Programme Grant)
Downes, P. (Investigator) & Leslie, N. (Investigator)
Medical Research Council
1/10/09 → 30/09/14
Project: Research

Cite this

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 et al. / 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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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)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",

author = "Davies, {Elizabeth M.} and Sheffield, {David A.} and Priyanka Tibarewal and Fedele, {Clare G.} and Mitchell, {Christina A.} and Leslie, {Nicholas R.}",

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language = "English",

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series = "Subcellular Biochemistry ",

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pages = "281--336",

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booktitle = "Phosphoinositides I",

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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 et al.
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 - Hydrolysis

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

U2 - 10.1007/978-94-007-3012-0_8

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

M3 - Chapter

C2 - 22403079

SN - 9789400730113

VL - 58

T3 - Subcellular Biochemistry

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EP - 336

BT - Phosphoinositides I

A2 - Balla, Tamas

A2 - Wymann, Matthias

A2 - York, John D.

PB - Springer Netherlands

CY - Dordrecht, Netherlands

ER -

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

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

Abstract

Publication series

Keywords

UN SDGs

Access to Document

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Projects

Aref#d: 21320. Antagonism of PI 3-Kinase Signalling by PTEN and SHIP2 (Programme Grant)

Cite this