Ligand-mediated autophosphorylation activity of the epidermal growth factor receptor during internalization

doi:10.1083/jcb.109.6.2751

This Article

	Full Text (PDF, 2013K)
	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 Lai, W. H.
	Articles by Bergeron, J. J.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Lai, W. H.
	Articles by Bergeron, J. J.


Social Bookmarking

	What's this?

ARTICLES

Ligand-mediated autophosphorylation activity of the epidermal growth factor receptor during internalization

WH Lai, PH Cameron, JJ Doherty 2d, BI Posner and JJ Bergeron
Department of Anatomy, McGill University, Montreal, Quebec, Canada.

The association of EGF with its receptor in endosomes isolated from rat liver homogenates was assessed biochemically by polyethylene glycol precipitation and morphologically by electron microscope radioautography. The proportion of receptor-bound ligand in endosomes at 15 min after the injection of doses of 0.1 and 1 microgram EGF/100 g body weight was 57%. This value increased to 77% for the dose of 10 micrograms EGF injected. Quantitative electron microscope radioautography carried out on endosomes isolated at 15 min after the injection of 10 micrograms 125I-EGF demonstrated that most radiolabel was over the endosomal periphery thereby indicating that ligand- receptor complexes were in the bounding membrane but not in intraluminal vesicles of the content. EGF receptor autophosphorylation activity during internalization was evaluated in plasmalemma and endosome fractions. This activity was markedly but transiently reduced on the cell surface shortly after the administration of saturating doses of EGF. The same activity, however, was augmented and prolonged in endosomes for up to 30 min after EGF injection. The transient desensitization of cell surface activity was not due to prior in vivo phosphorylation since receptor dephosphorylation in vitro failed to restore autophosphorylation activity. Transient desensitization of cell surface autophosphorylation activity coincided with a diminished capacity for endocytosis of 125I-EGF with endocytosis returning to normal after the restoration of cell surface autophosphorylation activity. The inhibition of cell surface autophosphorylation activity and the activation of endosomal autophosphorylation activity coincident with downregulation suggest that EGF receptor traffic is governed by ligand-regulated phosphorylation activity.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

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]
Singh, A. B., Sugimoto, K., Harris, R. C. (2007). Juxtacrine Activation of Epidermal Growth Factor (EGF) Receptor by Membrane-anchored Heparin-binding EGF-like Growth Factor Protects Epithelial Cells from Anoikis While Maintaining an Epithelial Phenotype. J. Biol. Chem. 282: 32890-32901 [Abstract] [Full Text]
Balbis, A., Parmar, A., Wang, Y., Baquiran, G., Posner, B. I. (2007). Compartmentalization of Signaling-Competent Epidermal Growth Factor Receptors in Endosomes. Endocrinology 148: 2944-2954 [Abstract] [Full Text]
Choi, J. H., Park, J. B., Bae, S. S., Yun, S., Kim, H. S., Hong, W.-P., Kim, I.-S., Kim, J. H., Han, M. Y., Ryu, S. H., Patterson, R. L., Snyder, S. H., Suh, P.-G. (2004). Phospholipase C-{gamma}1 is a guanine nucleotide exchange factor for dynamin-1 and enhances dynamin-1-dependent epidermal growth factor receptor endocytosis. J. Cell Sci. 117: 3785-3795 [Abstract] [Full Text]
Wang, Y., Pennock, S. D., Chen, X., Kazlauskas, A., Wang, Z. (2004). Platelet-derived Growth Factor Receptor-mediated Signal Transduction from Endosomes. J. Biol. Chem. 279: 8038-8046 [Abstract] [Full Text]
Pennock, S., Wang, Z. (2003). Stimulation of Cell Proliferation by Endosomal Epidermal Growth Factor Receptor As Revealed through Two Distinct Phases of Signaling. Mol. Cell. Biol. 23: 5803-5815 [Abstract] [Full Text]
McBain, V. A., Forrester, J. V., McCaig, C. D. (2003). HGF, MAPK, and a Small Physiological Electric Field Interact during Corneal Epithelial Cell Migration. IOVS 44: 540-547 [Abstract] [Full Text]
Wang, Y., Pennock, S., Chen, X., Wang, Z. (2002). Internalization of Inactive EGF Receptor into Endosomes and the Subsequent Activation of Endosome-Associated EGF Receptors. Sci Signal 2002: pl17-pl17 [Abstract] [Full Text]
Wang, Y., Pennock, S., Chen, X., Wang, Z. (2002). Endosomal Signaling of Epidermal Growth Factor Receptor Stimulates Signal Transduction Pathways Leading to Cell Survival. Mol. Cell. Biol. 22: 7279-7290 [Abstract] [Full Text]
Haugh, J. M. (2002). Localization of Receptor-Mediated Signal Transduction Pathways: The Inside Story. Mol. Interv. 2: 292-307 [Abstract] [Full Text]
Seto, E. S., Bellen, H. J., Lloyd, T. E. (2002). When cell biology meets development: endocytic regulation of signaling pathways. Genes Dev. 16: 1314-1336 [Full Text]
Jiang, X., Sorkin, A. (2002). Coordinated Traffic of Grb2 and Ras during Epidermal Growth Factor Receptor Endocytosis Visualized in Living Cells. Mol. Biol. Cell 13: 1522-1535 [Abstract] [Full Text]
Clague, M. J., Urbe, S. (2001). The interface of receptor trafficking and signalling. J. Cell Sci. 114: 3075-3081 [Abstract] [Full Text]
Oksvold, M. P., Skarpen, E., Lindeman, B., Roos, N., Huitfeldt, H. S. (2000). Immunocytochemical Localization of Shc and Activated EGF Receptor in Early Endosomes After EGF Stimulation of HeLa Cells. J. Histochem. Cytochem. 48: 21-34 [Abstract] [Full Text]
Haugh, J. M., Schooler, K., Wells, A., Wiley, H. S., Lauffenburger, D. A. (1999). Effect of Epidermal Growth Factor Receptor Internalization on Regulation of the Phospholipase C-gamma 1 Signaling Pathway. J. Biol. Chem. 274: 8958-8965 [Abstract] [Full Text]
Sorkina, T, Bild, A, Tebar, F, Sorkin, A (1999). Clathrin, adaptors and eps15 in endosomes containing activated epidermal growth factor receptors. J. Cell Sci. 112: 317-327 [Abstract]
Carter, R. E., Sorkin, A. (1998). Endocytosis of Functional Epidermal Growth Factor Receptor-Green Fluorescent Protein Chimera. J. Biol. Chem. 273: 35000-35007 [Abstract] [Full Text]
Maggi, D., Andraghetti, G., Carpentier, J.-L., Cordera, R. (1998). Cys860 in the Extracellular Domain of Insulin Receptor {beta}-Subunit Is Critical for Internalization and Signal Transduction. Endocrinology 139: 496-504 [Abstract] [Full Text]
Bevan, A. P., Krook, A., Tikerpae, J., Seabright, P. J., Siddle, K., Smith, G. D. (1997). Chloroquine Extends the Lifetime of the Activated Insulin Receptor Complex in Endosomes. J. Biol. Chem. 272: 26833-26840 [Abstract] [Full Text]
Komada, M., Masaki, R., Yamamoto, A., Kitamura, N. (1997). Hrs, a Tyrosine Kinase Substrate with a Conserved Double Zinc Finger Domain, Is Localized to the Cytoplasmic Surface of Early Endosomes. J. Biol. Chem. 272: 20538-20544 [Abstract] [Full Text]
Emlet, D. R., Moscatello, D. K., Ludlow, L. B., Wong, A. J. (1997). Subsets of Epidermal Growth Factor Receptors during Activation and Endocytosis. J. Biol. Chem. 272: 4079-4086 [Abstract] [Full Text]
Kornilova, E., Sorkina, T., Beguinot, L., Sorkin, A. (1996). Lysosomal Targeting of Epidermal Growth Factor Receptors via a Kinase-dependent Pathway Is Mediated by the Receptor Carboxyl-terminal Residues 1022-1123. J. Biol. Chem. 271: 30340-30346 [Abstract] [Full Text]
Bevan, A. P., Burgess, J. W., Drake, P. G., Shaver, A., Bergeron, J. J. M., Posner, B. I. (1995). Selective Activation of the Rat Hepatic Endosomal Insulin Receptor Kinase. J. Biol. Chem. 270: 10784-10791 [Abstract] [Full Text]
Gaulin, J.-F., Fiset, A., Fortier, S., Faure, R. L. (2000). Characterization of Cdk2-Cyclin E Complexes in Plasma Membrane and Endosomes of Liver Parenchyma. INSULIN-DEPENDENT REGULATION. J. Biol. Chem. 275: 16658-16665 [Abstract] [Full Text]
van Rossum, G. S. A. T., Klooster, R., van den Bosch, H., Verkleij, A. J., Boonstra, J. (2001). Phosphorylation of p42/44MAPK by Various Signal Transduction Pathways Activates Cytosolic Phospholipase A2 to Variable Degrees. J. Biol. Chem. 276: 28976-28983 [Abstract] [Full Text]