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.
KW - Charcot-Marie-Tooth Disease
KW - Gene Expression Regulation
KW - Humans
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
SP - 281
EP - 336
BT - Phosphoinositides I
A2 - Balla, Tamas
A2 - Wymann, Matthias
A2 - York, John D.
PB - Springer Netherlands
CY - Dordrecht, Netherlands
ER -
