Egf And Tgf-alpha Motogenic Activities Are Mediated by the Egf Receptor Via Distinct Matrix-dependent Mechanisms.
From: Unit of Cell and Molecular Biology, The Dental School, University of Dundee, Dundee DD1 4HR, Scotland, UK.
Experimental cell research
- Publish Date: Feb 2007
- ISSN: 0014-4827
- Volume: 313
- Issue: 4
- Pages: 732-41
- Medium: Print
- Language: English
- Citation (JAMA): Ellis Ian R, Schor Ana M, Schor Seth L, et al. Egf And Tgf-alpha Motogenic Activities Are Mediated by the Egf Receptor Via Distinct Matrix-dependent Mechanisms.. Exp. Cell Res. Feb 2007;313:732-41
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(S6K) participating in EGF signalling and phospholipase Cgamma 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 alphavbeta3. 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 alphavbeta3 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.
Mesh Headings (Keywords): Antigens, CD44, Cell Movement, Cells, Cultured, Epidermal Growth Factor, Extracellular Matrix, Humans, Hyaluronic Acid, Integrin alphaVbeta3, Models, Biological, Receptor, Epidermal Growth Factor, Signal Transduction, Transforming Growth Factor alpha
Check for Full Text / PubMed Unique Identifier (PMID): 17196962
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