The lipid phosphatase, PTEN (phosphatase and tensin homologue deleted on chromosome 10), is the product of a major tumour suppressor gene that antagonizes PI3K (phosphoinositide 3-kinase) signalling by dephosphorylating the 3-position of the inositol ring of PtdIns(3,4,5)P3. PtdIns(3,4,5)P3 is also metabolized by removal of the 5-phosphate catalysed by a distinct family of enzymes exemplified by SHIP1 [SH2 (Src homology 2)-containing inositol phosphatase 1] and SHIP2. Mouse knockout studies, however, suggest that PTEN and SHIP2 have profoundly different biological functions. One important reason for this is likely to be that SHIP2 exists in a relatively inactive state until cells are exposed to growth factors or other stimuli. Hence, regulation of SHIP2 is geared towards stimulus dependent antagonism of PI3K signalling. PTEN, on the other hand, appears to be active in unstimulated cells and functions to maintain basal PtdIns(3,4,5)P3 levels below the critical signalling threshold. We suggest that concomitant inhibition of cysteine-dependent phosphatases, such as PTEN, with activation of SHIP2 functions as a metabolic switch to regulate independently the relative levels of PtdIns(3,4,5)P3 and PtdIns(3,4)P2.
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Conference Article|
March 20 2007
Metabolic switching of PI3K-dependent lipid signals
C.P. Downes;
C.P. Downes
1
1Division of Molecular Physiology, James Black Centre, College of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K.
1To whom correspondence should be addressed (email c.p.downes@dundee.ac.uk).
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N.R. Leslie;
N.R. Leslie
1Division of Molecular Physiology, James Black Centre, College of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K.
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I.H. Batty;
I.H. Batty
1Division of Molecular Physiology, James Black Centre, College of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K.
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J. van der Kaay
J. van der Kaay
1Division of Molecular Physiology, James Black Centre, College of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K.
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Publisher: Portland Press Ltd
Received:
October 20 2006
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2007 The Biochemical Society
2007
Biochem Soc Trans (2007) 35 (2): 188–192.
Article history
Received:
October 20 2006
Citation
C.P. Downes, N.R. Leslie, I.H. Batty, J. van der Kaay; Metabolic switching of PI3K-dependent lipid signals. Biochem Soc Trans 1 April 2007; 35 (2): 188–192. doi: https://doi.org/10.1042/BST0350188
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