CG&D
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Donato, N. J.
Right arrow Articles by Steck, P. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Donato, N. J.
Right arrow Articles by Steck, P. A.

Cell Growth & Differentiation, Vol 3, Issue 5 259-268, Copyright © 1992 by American Association of Cancer Research


ARTICLES

Tumor necrosis factor regulates tyrosine phosphorylation on epidermal growth factor receptors in A431 carcinoma cells: evidence for a distinct mechanism

NJ Donato, MG Rosenblum and PA Steck
Department of Clinical Immunology, M. D. Anderson Cancer Center, Houston, Texas 77030.

Previous studies of tumor necrosis factor (TNF) action on tumor cells revealed a possible role for tyrosine phosphorylation of epidermal growth factor (EGF) receptor in the growth-regulatory activities of this cytokine (N. J. Donato, G. E. Gallick, P. A. Steck, and M. G. Rosenblum, J. Biol. Chem., 264: 20474-20481, 1989). EGF receptor immunoprecipitated from [32P] phosphate-equilibrated A431 cells demonstrated that TNF treatment resulted in both a time- and concentration-dependent stimulation of EGF receptor phosphorylation, which was maximal (approximately 3-fold) after 10-20 min of TNF exposure (10 nM). Incubation of A431 cells with an equivalent concentration of EGF resulted in similar stimulation of EGF receptor phosphorylation, albeit at different phosphotyrosine levels. Antiphosphotyrosine immunoblot analysis confirmed these results but suggested that the extent and kinetics of TNF-induced tyrosine phosphorylation were distinct from those obtained in EGF-treated cells. Resolution of tryptic phosphopeptides from EGF receptor demonstrated that TNF-induced phosphorylation of EGF receptor was similar, but not identical, to profiles obtained from EGF-treated cells and distinct when compared to the actions of phorbol ester. Unlike EGF, TNF was unable to directly stimulate EGF receptor tyrosine kinase activity in membranes prepared from A431 cells. In addition, TNF treatment had no significant effect on either the high- or low-affinity ligand-binding sites on EGF receptor and did not alter the kinetics or extent of ligand-induced internalization of EGF receptors. However, EGF receptor biosynthesis was consistently increased upon prolonged treatment with TNF (4-12 h). Our results suggest that TNF regulates both phosphorylation and biosynthesis of EGF receptor in a manner distinct from that of both EGF and phorbol ester, and studies of the differential phosphorylation of EGF receptor may aid in understanding the molecular mode of TNF action.


This article has been cited by other articles:


Home page
Proc. Natl. Acad. Sci. USAHome page
K. Takeyama, K. Dabbagh, H.-M. Lee, C. Agusti, J. A. Lausier, I. F. Ueki, K. M. Grattan, and J. A. Nadel
Epidermal growth factor system regulates mucin production in airways
PNAS, March 16, 1999; 96(6): 3081 - 3086.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
D.-i. Jeoung, B. Tang, and M. Sonenberg
Effects of Tumor Necrosis Factor-{alpha} on Antimitogenicity and Cell Cycle-related Proteins in MCF-7 Cells
J. Biol. Chem., August 4, 1995; 270(31): 18367 - 18373.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 1992 by the American Association of Cancer Research.