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Molecular and Cellular Biology, March 2005, p. 2347-2363, Vol. 25, No. 6
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.6.2347-2363.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Phosphoinositide-Dependent Phosphorylation of PDK1 Regulates Nuclear Translocation

Michael P. Scheid,1* Michael Parsons,1 and James R. Woodgett1,2

University Health Network, Princess Margaret Hospital,1 Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada2

Received 9 September 2004/ Returned for modification 27 October 2004/ Accepted 30 November 2004

3-Phosphoinositide-dependent kinase 1 (PDK1) phosphorylates the activation loop of a number of protein serine/threonine kinases of the AGC kinase superfamily, including protein kinase B (PKB; also called Akt), serum and glucocorticoid-induced kinase, protein kinase C isoforms, and the p70 ribosomal S6 kinase. PDK1 contains a carboxyl-terminal pleckstrin homology domain, which targets phosphoinositide lipids at the plasma membrane and is central to the activation of PKB. However, PDK1 subcellular trafficking to other compartments is not well understood. We monitored the posttranslational modifications of PDK1 following insulin-like growth factor 1 stimulation. PDK1 underwent rapid and transient phosphorylation on S396, which was dependent upon plasma membrane localization. Phosphorylation of S396 was necessary for nuclear shuttling of PDK1, possibly through its influence on an adjacent nuclear export sequence. Thus, mitogen-stimulated phosphorylation of PDK1 provides a means for directed PDK1 subcellular trafficking, with potential implications for PDK1 signaling.

* Corresponding author. Present address: Department of Biology, York University, Toronto, Ontario, Canada M3J 1P3. Phone: (417) 736-2100, ext. 40069. Fax: (416) 736-5698. E-mail: mscheid{at}yorku.ca.

Molecular and Cellular Biology, March 2005, p. 2347-2363, Vol. 25, No. 6
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.6.2347-2363.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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