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J. Biol. Chem., Vol. 283, Issue 5, 2465-2469, February 1, 2008

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Minireview

Phosphoinositide Lipid Phosphatases: Natural Regulators of Phosphoinositide 3-Kinase Signaling in T Lymphocytes^*

Stephanie J. Harris¹, Richard V. Parry, John Westwick, and Stephen G. Ward²

From the Inflammatory Cell Biology Laboratory, Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, United Kingdom and the Respiratory Disease Area, Novartis Institute for BioMedical Research, Wimblehurst Road, Horsham, West Sussex RH12 5AB, United Kingdom

The phosphoinositide 3-kinase signaling pathway has been implicated in a range of T lymphocyte cellular functions, particularly growth, proliferation, cytokine secretion, and survival. Dysregulation of phosphoinositide 3-kinase-dependent signaling and function in leukocytes, including B and T lymphocytes, has been implicated in many inflammatory and autoimmune diseases. As befits a pivotal signaling cascade, several mechanisms exist to ensure that the pathway is tightly regulated. This minireview focuses on two lipid phosphatases, viz. the 3'-phosphatase PTEN (phosphatase and tensin homolog deleted on chromosome 10) and SHIP (Src homology 2 domain-containing inositol-5-phosphatase). We discuss their role in regulating T lymphocyte signaling as well their potential as future therapeutic targets.

^* This minireview will be reprinted in the 2008 Minireview Compendium, which will be available in January, 2009.

¹ Recipient of a Biotechnology and Biological Sciences Research Council doctoral training award.

² Royal Society Industrial Fellow. To whom correspondence should be addressed. E-mail: s.g.ward{at}bath.ac.uk.

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