Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 613K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef 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?

© The Rockefeller University Press, 0021-9525/2000//539 $5.00
The Journal of Cell Biology, Volume 151, Number 3, , 2000 539-550

Epidermal Growth Factor and Membrane Trafficking

M. Alejandro Barbieri^a, Richard L. Roberts^a, Aysel Gumusboga^a, Hilary Highfield^a, Carmen Alvarez-Dominguez^b, Alan Wells^c, and Philip D. Stahl^a

^a Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110
^b Centro de Biologia Molecular SEVERO OCHOA, 28033 Madrid, Spain
^c Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261
Department of Cell Biology and Physiology, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110.(314) 362-1490(314) 362-6950

Activated epidermal growth factor receptors recruit various intracellular proteins leading to signal generation and endocytic trafficking. Although activated receptors are rapidly internalized into the endocytic compartment and subsequently degraded in lysosomes, the linkage between signaling and endocytosis is not well understood. Here we show that EGF stimulation of NR6 cells induces a specific, rapid and transient activation of Rab5a. EGF also enhanced translocation of the Rab5 effector, early endosomal autoantigen 1 (EEA1), from cytosol to membrane. The activation of endocytosis, fluid phase and receptor mediated, by EGF was enhanced by Rab5a expression, but not by Rab5b, Rab5c, or Rab5a truncated at the NH₂ and/or COOH terminus. Dominant negative Rab5a (Rab5:N34) blocked EGF-stimulated receptor-mediated and fluid-phase endocytosis. EGF activation of Rab5a function was dependent on tyrosine residues in the COOH-terminal domain of the EGF receptor (EGFR). Removal of the entire COOH terminus by truncation (c'973 and c'991) abrogated ligand-induced Rab5a activation of endocytosis. A "kinase-dead" EGFR failed to stimulate Rab5a function. However, another EGF receptor mutant (c'1000), with the kinase domain intact and a single autophosphorylation site effectively signaled Rab5 activation. These results indicate that EGFR and Rab5a are linked via a cascade that results in the activation of Rab5a and that appears essential for internalization. The results point to an interdependent relationship between receptor activation, signal generation and endocytosis.

Key Words: signal transduction • endocytosis • Rab5 • endosome • fusion

© 2000 The Rockefeller University Press

CiteULike

Complore

Connotea

Del.icio.us

Digg

Facebook

Reddit

Technorati

Twitter

This article has been cited by other articles:

• Chen, P.-I, Kong, C., Su, X., Stahl, P. D. (2009). Rab5 Isoforms Differentially Regulate the Trafficking and Degradation of Epidermal Growth Factor Receptors. J. Biol. Chem. 284: 30328-30338 [Abstract] [Full Text]  
• Tomshine, J. C., Severson, S. R., Wigle, D. A., Sun, Z., Beleford, D. A. T., Shridhar, V., Horazdovsky, B. F. (2009). Cell Proliferation and Epidermal Growth Factor Signaling in Non-small Cell Lung Adenocarcinoma Cell Lines Are Dependent on Rin1. J. Biol. Chem. 284: 26331-26339 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents