RRC ID 64422
Author Yoshizaki H, Mochizuki N, Gotoh Y, Matsuda M.
Title Akt-PDK1 complex mediates epidermal growth factor-induced membrane protrusion through Ral activation.
Journal Mol Biol Cell
Abstract 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.
Volume 18(1)
Pages 119-28
Published 2007-1-1
DOI 10.1091/mbc.e06-05-0467
PII E06-05-0467
PMID 17079732
PMC PMC1751317
MeSH 3-Phosphoinositide-Dependent Protein Kinases Animals COS Cells Cell Membrane / drug effects Chlorocebus aethiops Epidermal Growth Factor / pharmacology* Fluorescence Resonance Energy Transfer Immunoprecipitation Mice Multienzyme Complexes / metabolism* NIH 3T3 Cells Phosphatidylinositol Phosphates / metabolism Protein Binding / drug effects Protein Serine-Threonine Kinases / metabolism* Protein Transport / drug effects Proto-Oncogene Proteins c-akt / metabolism* Pseudopodia / drug effects* ral GTP-Binding Proteins / metabolism* ral Guanine Nucleotide Exchange Factor / metabolism*
IF 3.791
Human and Animal Cells NIH 3T3