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¹ Division of Immunology and Cell Biology, University of Dundee, Dundee DD15EH, Scotland, UK
² Department of Molecular Biology, Genentech, Inc., South San Francisco, CA 94080
³ AMC Liver Center, Academic Medical Center S1-162, 1105BK Amsterdam, Netherlands

CORRESPONDENCE Doreen A. Cantrell: d.a.cantrell{at}dundee.ac.uk

In normal T cell progenitors, phosphoinositide-dependent kinase l (PDK1)–mediated phosphorylation and activation of protein kinase B (PKB) is essential for the phosphorylation and inactivation of Foxo family transcription factors, and also controls T cell growth and proliferation. The current study has characterized the role of PDK1 in the pathology caused by deletion of the tumor suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN). PDK1 is shown to be essential for lymphomagenesis caused by deletion of PTEN in T cell progenitors. However, PTEN deletion bypasses the normal PDK1-controlled signaling pathways that determine thymocyte growth and proliferation. PDK1 does have important functions in PTEN-null thymocytes, notably to control the PKB–Foxo signaling axis and to direct the repertoire of adhesion and chemokine receptors expressed by PTEN-null T cells. The results thus provide two novel insights concerning pathological signaling caused by PTEN loss in lymphocytes. First, PTEN deletion bypasses the normal PDK1-controlled metabolic checkpoints that determine cell growth and proliferation. Second, PDK1 determines the cohort of chemokine and adhesion receptors expressed by PTEN-null cells, thereby controlling their migratory capacity.

Abbreviations used: CMTMR, 5-(and-6)-(((4-chloromethyl)benzoyl)amino)tetramethylrhodamine; DN, double negative; DP, double positive; KLF2, Kruppel-like factor 2; mTOR, mammalian target of rapamycin; PDK1, phosphoinositide-dependent kinase l; PI3K, phosphoinositide 3-kinase; PI(3,4,5)P₃, phosphoinositide (3,4,5) trisphosphate; PKB, protein kinase B; PTEN, phosphatase and tensin homologue deleted on chromosome 10; SP, single positive.

© 2009 Finlay et al.
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This article has been cited by other articles:

• Finlay, D. K., Sinclair, L. V., Feijoo, C., Waugh, C. M., Hagenbeek, T. J., Spits, H., Cantrell, D. A. (2009). Phosphoinositide-dependent kinase 1 controls migration and malignant transformation but not cell growth and proliferation in PTEN-null lymphocytes. JCB 187: i1-i1 [Full Text]  

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