EGF AND TGF-α motogenic activities are mediated by the EGF receptor via distinct matrix-dependent mechanisms

Ian R. Ellis, Ana M. Schor, Seth L. Schor

    Research output: Contribution to journalArticlepeer-review

    32 Citations (Scopus)

    Abstract

    EGF and TGF-a 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 p70S6K participating in EGF signalling and phospholipase C? in TGF-a signalling. We additionally demonstrate that EGF and TGF-a 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-a requires EGFR and integrin avß3. 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-a. In contrast, the mitogenic activities of EGF and TGF-a are independent of CD44 and avß3 functionality. These results demonstrate clear qualitative differences between EGF and TGF-a pathways and highlight the importance of the extracellular matrix in regulating cytokine bioactivity.
    Original languageEnglish
    Pages (from-to)732-741
    Number of pages10
    JournalExperimental Cell Research
    Volume313
    Issue number4
    DOIs
    Publication statusPublished - 15 Feb 2007

    Keywords

    • EGF
    • TGF-α
    • Extracellular matrix
    • Signal transduction
    • Cell motility
    • Hyaluronan
    • Vitronectin
    • CD44
    • αvβ3
    • Phospholipase Cγ
    • p70s6k

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