HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend 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 Barbieri, M. A. Articles by Stahl, P. D. Search for Related Content PubMed PubMed Citation Articles by Barbieri, M. A. Articles by Stahl, P. D. Social Bookmarking                      What's this?

J Biol Chem, Vol. 273, Issue 31, 19367-19370, July 31, 1998

COMMUNICATION
Protein Kinase B/akt and Rab5 Mediate Ras Activation of Endocytosis

M. Alejandro Barbieri, Aimee D. Kohn^¶, Richard A. Roth^¶, and Philip D. Stahl

From the  Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110 and the ^¶ Department of Molecular Pharmacology, Stanford University School of Medicine, Palo Alto, California 94305

Transient expression of oncogenic Ha-Ras (Ras:V12) stimulates endocytosis. Using NIH3T3 cells expressing constitutively active protein kinase B/akt (PKB/akt) or kinase-dead PKB/akt, we show that PKB/akt mediates the stimulatory effect of Ras on endocytosis. Fluid phase endocytosis of horseradish peroxidase in cells expressing the constitutively active form of PKB/akt was elevated and insensitive to phosphatidylinositol 3-kinase inhibitors. However, expression of dominant negative Rab5:N34 blocked endocytosis in cells expressing the constitutively active form of PKB/akt.

Transient expression of either Rab5:wt or Rab5:L79, a GTPase deficient mutant of Rab5, in cells expressing constitutively activated PKB/akt further increased endocytic rate. However, in cells expressing kinase-dead PKB/akt, endocytic rate was not affected by transient expression of Rab5:wt. Rab5:L79, on the other hand, increased endocytosis in cells expressing kinase-dead PKB/akt. Similar results were obtained using an in vitro endosome fusion reconstitution assay with cytosol prepared from cells expressing the activated PKB/akt or kinase-dead PKB/akt. Both Rab5:wt and Rab5:L79 stimulated endosome fusion when assayed in cytosol containing the activated PKB/akt, whereas only Rab5:L79 activated fusion when the assay utilized cytosol from kinase-dead expressing cells. We conclude that Ras activation of endocytosis requires both PKB/akt and Rab5 and that active kinase is required for activation Rab5.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				N. Porat-Shliom, Y. Kloog, and J. G. Donaldson A Unique Platform for H-Ras Signaling Involving Clathrin-independent Endocytosis Mol. Biol. Cell, March 1, 2008; 19(3): 765 - 775. [Abstract] [Full Text] [PDF]

				M. Stone, S. Jia, W. D. Heo, T. Meyer, and K. V. Konan Participation of Rab5, an Early Endosome Protein, in Hepatitis C Virus RNA Replication Machinery J. Virol., May 1, 2007; 81(9): 4551 - 4563. [Abstract] [Full Text] [PDF]

				G. A. Lang and M. L. Lang Protein Kinase B{alpha} Is Required for Vesicle Trafficking and Class II Presentation of IgA Fc Receptor (CD89)-Targeted Antigen J. Immunol., April 1, 2006; 176(7): 3987 - 3994. [Abstract] [Full Text] [PDF]

				J. Kalesnikoff, E. J. Rios, C.-C. Chen, S. Nakae, B. A. Zabel, E. C. Butcher, M. Tsai, S.-Y. Tam, and S. J. Galli RabGEF1 regulates stem cell factor/c-Kit-mediated signaling events and biological responses in mast cells. PNAS, February 21, 2006; 103(8): 2659 - 2664. [Abstract] [Full Text] [PDF]

				D. C. Berwick, G. C. Dell, G. I. Welsh, K. J. Heesom, I. Hers, L. M. Fletcher, F. T. Cooke, and J. M. Tavare Protein kinase B phosphorylation of PIKfyve regulates the trafficking of GLUT4 vesicles J. Cell Sci., December 1, 2004; 117(25): 5985 - 5993. [Abstract] [Full Text] [PDF]

				E. Stang, F. D. Blystad, M. Kazazic, V. Bertelsen, T. Brodahl, C. Raiborg, H. Stenmark, and I. H. Madshus Cbl-dependent Ubiquitination Is Required for Progression of EGF Receptors into Clathrin-coated Pits Mol. Biol. Cell, August 1, 2004; 15(8): 3591 - 3604. [Abstract] [Full Text] [PDF]

				M. S. Roberts, A. J. Woods, T. C. Dale, P. van der Sluijs, and J. C. Norman Protein Kinase B/Akt Acts via Glycogen Synthase Kinase 3 To Regulate Recycling of {alpha}v{beta}3 and {alpha}5{beta}1 Integrins Mol. Cell. Biol., February 15, 2004; 24(4): 1505 - 1515. [Abstract] [Full Text] [PDF]

				M. A. Barbieri, C. Kong, P.-I Chen, B. F. Horazdovsky, and P. D. Stahl The Src Homology 2 Domain of Rin1 Mediates Its Binding to the Epidermal Growth Factor Receptor and Regulates Receptor Endocytosis J. Biol. Chem., August 22, 2003; 278(34): 32027 - 32036. [Abstract] [Full Text] [PDF]

				S. J. Grille, A. Bellacosa, J. Upson, A. J. Klein-Szanto, F. van Roy, W. Lee-Kwon, M. Donowitz, P. N. Tsichlis, and L. Larue The Protein Kinase Akt Induces Epithelial Mesenchymal Transition and Promotes Enhanced Motility and Invasiveness of Squamous Cell Carcinoma Lines Cancer Res., May 1, 2003; 63(9): 2172 - 2178. [Abstract] [Full Text] [PDF]

				S. Roy, B. Wyse, and J. F. Hancock H-Ras Signaling and K-Ras Signaling Are Differentially Dependent on Endocytosis Mol. Cell. Biol., July 15, 2002; 22(14): 5128 - 5140. [Abstract] [Full Text] [PDF]

				N. Segev Ypt/Rab GTPases: Regulators of Protein Trafficking Sci. Signal., September 18, 2001; 2001(100): re11 - re11. [Abstract] [Full Text] [PDF]

				A. Rupper, K. Lee, D. Knecht, and J. Cardelli Sequential Activities of Phosphoinositide 3-Kinase, PKB/Akt, and Rab7 during Macropinosome Formation in Dictyostelium Mol. Biol. Cell, September 1, 2001; 12(9): 2813 - 2824. [Abstract] [Full Text] [PDF]

				M. L. Lang, L. Shen, H. Gao, W. F. Cusack, G. A. Lang, and W. F. Wade Fc{{alpha}} Receptor Cross-Linking Causes Translocation of Phosphatidylinositol-Dependent Protein Kinase 1 and Protein Kinase B{{alpha}} to MHC Class II Peptide-Loading-Like Compartments J. Immunol., May 1, 2001; 166(9): 5585 - 5593. [Abstract] [Full Text] [PDF]

				M. Symons and Y. Takai Ras GTPases: Singing in Tune Sci. Signal., February 6, 2001; 2001 (68): pe1 - pe1. [Abstract] [Full Text] [PDF]

				M. J. Clague and S. Urbe The interface of receptor trafficking and signalling J. Cell Sci., January 9, 2001; 114(17): 3075 - 3081. [Abstract] [Full Text] [PDF]

				A. Rupper, J. Rodriguez-Paris, B. Grove, and J. Cardelli p110-related PI 3-kinases regulate phagosome-phagosome fusion and phagosomal pH through a PKB/Akt dependent pathway in Dictyostelium J. Cell Sci., January 4, 2001; 114(7): 1283 - 1295. [Abstract] [PDF]

				X. Zi, R. P. Singh, and R. Agarwal Impairment of erbB1 receptor and fluid-phase endocytosis and associated mitogenic signaling by inositol hexaphosphate in human prostate carcinoma DU145 cells Carcinogenesis, December 1, 2000; 21(12): 2225 - 2235. [Abstract] [Full Text] [PDF]

				R. L. Roberts, M. A. Barbieri, J. Ullrich, and P. D. Stahl Dynamics of rab5 activation in endocytosis and phagocytosis J. Leukoc. Biol., November 1, 2000; 68(5): 627 - 632. [Abstract] [Full Text]

				M. Barbieri, R. Roberts, Gumusboga, Highfield, Alvarez-Dominguez, Wells, and P. Stahl Epidermal Growth Factor and Membrane Trafficking: EGF Receptor Activation of Endocytosis Requires Rab5a J. Cell Biol., October 30, 2000; 151(3): 539 - 550. [Abstract] [Full Text] [PDF]

				C Prevostel, V Alice, D Joubert, and P. Parker Protein kinase C(alpha) actively downregulates through caveolae-dependent traffic to an endosomal compartment J. Cell Sci., January 7, 2000; 113(14): 2575 - 2584. [Abstract] [PDF]

				J Somsel Rodman and A Wandinger-Ness Rab GTPases coordinate endocytosis J. Cell Sci., January 1, 2000; 113(2): 183 - 192. [Abstract] [PDF]

				L. Bertrand, D. R. Alessi, J. Deprez, M. Deak, E. Viaene, M. H. Rider, and L. Hue Heart 6-Phosphofructo-2-kinase Activation by Insulin Results from Ser-466 and Ser-483 Phosphorylation and Requires 3-Phosphoinositide-dependent Kinase-1, but Not Protein Kinase B J. Biol. Chem., October 22, 1999; 274(43): 30927 - 30933. [Abstract] [Full Text] [PDF]

				T. Kitamura, Y. Kitamura, S. Kuroda, Y. Hino, M. Ando, K. Kotani, H. Konishi, H. Matsuzaki, U. Kikkawa, W. Ogawa, et al. Insulin-Induced Phosphorylation and Activation of Cyclic Nucleotide Phosphodiesterase 3B by the Serine-Threonine Kinase Akt Mol. Cell. Biol., September 1, 1999; 19(9): 6286 - 6296. [Abstract] [Full Text] [PDF]

				A. V. Bakin, A. K. Tomlinson, N. A. Bhowmick, H. L. Moses, and C. L. Arteaga Phosphatidylinositol 3-Kinase Function Is Required for Transforming Growth Factor beta -mediated Epithelial to Mesenchymal Transition and Cell Migration J. Biol. Chem., November 17, 2000; 275(47): 36803 - 36810. [Abstract] [Full Text] [PDF]

				M. A. Rizzo, C. A. Kraft, S. C. Watkins, E. S. Levitan, and G. Romero Agonist-dependent Traffic of Raft-associated Ras and Raf-1 Is Required for Activation of the Mitogen-activated Protein Kinase Cascade J. Biol. Chem., September 7, 2001; 276(37): 34928 - 34933. [Abstract] [Full Text] [PDF]

				A. K.A. deHart, J. D. Schnell, D. A. Allen, and L. Hicke The conserved Pkh-Ypk kinase cascade is required for endocytosis in yeast J. Cell Biol., January 21, 2002; 156(2): 241 - 248. [Abstract] [Full Text] [PDF]