QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 18, Issue 1, 119-128, January 2007

This Article Full Text Full Text (PDF) Supplemental Material All Versions of this Article: E06-05-0467v1 18/1/119    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yoshizaki, H. Articles by Matsuda, M. Search for Related Content PubMed PubMed Citation Articles by Yoshizaki, H. Articles by Matsuda, M.

Akt–PDK1 Complex Mediates Epidermal Growth Factor-induced Membrane Protrusion through Ral Activation

Hisayoshi Yoshizaki^*,, Naoki Mochizuki^*, Yukiko Gotoh, and Michiyuki Matsuda

*Department of Structural Analysis, National Cardiovascular Center Research Institute, Osaka 565-8565, Japan; Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan; and Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo 113-0032, Japan

Submitted May 31, 2006; Revised October 16, 2006; Accepted October 19, 2006
Monitoring Editor: Martin A. Schwartz

We studied the spatiotemporal regulation of Akt (also called protein kinase B), phosphatidylinositol-3,4-bisphosphate [PtdIns(3,4)P₂], and phosphatidylinositol-3,4,5-trisphosphate [PtdIns(3,4,5)P₃] by using probes based on the principle of fluorescence resonance energy transfer. On epidermal growth factor (EGF) stimulation, the amount of PtdIns(3,4,5)P₃ was increased diffusely in the plasma membrane, whereas that of PtdIns(3,4)P₂ was increased more in the nascent lamellipodia than in the plasma membrane of the central region. The distribution and time course of Akt activation were similar to that of increased PtdIns(3,4)P₂ levels, which were most prominent in the nascent lamellipodia. Moreover, we found that upon EGF stimulation 3-phosphoinositide–dependent protein kinase-1 (PDK1) was also recruited to nascent lamellipodia in an Akt-dependent manner. Because PDK1 is known to activate Ral GTPase and because Ral is required for EGF-induced lamellipodial protrusion, we speculated that the PDK1–Akt complex may be indispensable for the induction of lamellipodia. In agreement with this idea, EGF-induced lamellipodia formation was promoted by the overexpression of Akt and inhibited by an Akt inhibitor or a Ral-binding domain of Sec5. These results identified the Akt–PDK1 complex as an upstream positive regulator of Ral GTPase in the induction of lamellipodial protrusion.

This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E06-05-0467) on November 1, 2006.

Address correspondence to: Michiyuki Matsuda (matsudam{at}path1.med.kyoto-u.ac.jp)

This article has been cited by other articles:

				T. Nishioka, K. Aoki, K. Hikake, H. Yoshizaki, E. Kiyokawa, and M. Matsuda Rapid Turnover Rate of Phosphoinositides at the Front of Migrating MDCK Cells Mol. Biol. Cell, October 1, 2008; 19(10): 4213 - 4223. [Abstract] [Full Text] [PDF]

				Y. Hao, R. Wong, and L. A. Feig RalGDS Couples Growth Factor Signaling to Akt Activation Mol. Cell. Biol., May 1, 2008; 28(9): 2851 - 2859. [Abstract] [Full Text] [PDF]

				K. Aoki, T. Nakamura, T. Inoue, T. Meyer, and M. Matsuda An essential role for the SHIP2-dependent negative feedback loop in neuritogenesis of nerve growth factor-stimulated PC12 cells J. Cell Biol., June 21, 2007; 177(5): 817 - 827. [Abstract] [Full Text] [PDF]