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Title: EGF AND TGF-{alpha} motogenic activities are mediated by the EGF receptor via distinct matrix-dependent mechanisms

Abstract

EGF and TGF-{alpha} induce an equipotent stimulation of fibroblast migration and proliferation. In spite of their homologous structure and ligation by the same receptor (EGFR), we report that their respective motogenic activities are mediated by different signal transduction intermediates, with p70{sup S6K} participating in EGF signalling and phospholipase C{gamma} in TGF-{alpha} signalling. We additionally demonstrate that EGF and TGF-{alpha} motogenic activities may be resolved into two stages: (a) cell 'activation' by a transient exposure to either cytokine, and (b) the subsequent 'manifestation' of an enhanced migratory phenotype in the absence of cytokine. The cell activation and manifestation stages for each cytokine are mediated by distinct matrix-dependent mechanisms: motogenetic activation by EGF requires the concomitant functionality of EGFR and the hyaluronan receptor CD44, whereas activation by TGF-{alpha} requires EGFR and integrin {alpha}v{beta}3. Manifestation of elevated migration no longer requires the continued presence of exogenous cytokine and functional EGFR but does require the above mentioned matrix receptors, as well as their respective ligands, i.e., hyaluronan in the case of EGF, and vitronectin in the case of TGF-{alpha}. In contrast, the mitogenic activities of EGF and TGF-{alpha} are independent of CD44 and {alpha}v{beta}3 functionality. These results demonstrate clear qualitative differences between EGF andmore » TGF-{alpha} pathways and highlight the importance of the extracellular matrix in regulating cytokine bioactivity.« less

Authors:
 [1];  [1];  [2]
  1. Unit of Cell and Molecular Biology, Dental School, University of Dundee, Dundee DD1 4HR, Scotland (United Kingdom)
  2. Unit of Cell and Molecular Biology, Dental School, University of Dundee, Dundee DD1 4HR, Scotland (United Kingdom). E-mail: s.l.schor@dundee.ac.uk
Publication Date:
OSTI Identifier:
20972120
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 313; Journal Issue: 4; Other Information: DOI: 10.1016/j.yexcr.2006.11.016; PII: S0014-4827(06)00479-4; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CELL PROLIFERATION; FIBROBLASTS; LIGANDS; MATRICES; PHENOTYPE; RECEPTORS; STIMULATION

Citation Formats

Ellis, Ian R., Schor, Ana M., and Schor, Seth L. EGF AND TGF-{alpha} motogenic activities are mediated by the EGF receptor via distinct matrix-dependent mechanisms. United States: N. p., 2007. Web. doi:10.1016/j.yexcr.2006.11.016.
Ellis, Ian R., Schor, Ana M., & Schor, Seth L. EGF AND TGF-{alpha} motogenic activities are mediated by the EGF receptor via distinct matrix-dependent mechanisms. United States. doi:10.1016/j.yexcr.2006.11.016.
Ellis, Ian R., Schor, Ana M., and Schor, Seth L. Thu . "EGF AND TGF-{alpha} motogenic activities are mediated by the EGF receptor via distinct matrix-dependent mechanisms". United States. doi:10.1016/j.yexcr.2006.11.016.
@article{osti_20972120,
title = {EGF AND TGF-{alpha} motogenic activities are mediated by the EGF receptor via distinct matrix-dependent mechanisms},
author = {Ellis, Ian R. and Schor, Ana M. and Schor, Seth L.},
abstractNote = {EGF and TGF-{alpha} induce an equipotent stimulation of fibroblast migration and proliferation. In spite of their homologous structure and ligation by the same receptor (EGFR), we report that their respective motogenic activities are mediated by different signal transduction intermediates, with p70{sup S6K} participating in EGF signalling and phospholipase C{gamma} in TGF-{alpha} signalling. We additionally demonstrate that EGF and TGF-{alpha} motogenic activities may be resolved into two stages: (a) cell 'activation' by a transient exposure to either cytokine, and (b) the subsequent 'manifestation' of an enhanced migratory phenotype in the absence of cytokine. The cell activation and manifestation stages for each cytokine are mediated by distinct matrix-dependent mechanisms: motogenetic activation by EGF requires the concomitant functionality of EGFR and the hyaluronan receptor CD44, whereas activation by TGF-{alpha} requires EGFR and integrin {alpha}v{beta}3. Manifestation of elevated migration no longer requires the continued presence of exogenous cytokine and functional EGFR but does require the above mentioned matrix receptors, as well as their respective ligands, i.e., hyaluronan in the case of EGF, and vitronectin in the case of TGF-{alpha}. In contrast, the mitogenic activities of EGF and TGF-{alpha} are independent of CD44 and {alpha}v{beta}3 functionality. These results demonstrate clear qualitative differences between EGF and TGF-{alpha} pathways and highlight the importance of the extracellular matrix in regulating cytokine bioactivity.},
doi = {10.1016/j.yexcr.2006.11.016},
journal = {Experimental Cell Research},
number = 4,
volume = 313,
place = {United States},
year = {Thu Feb 15 00:00:00 EST 2007},
month = {Thu Feb 15 00:00:00 EST 2007}
}