Main Menu (Mobile)- Block

Main Menu - Block

janelia7_blocks-janelia7_secondary_menu | block
More in this page
janelia7_blocks-janelia7_fake_breadcrumb | block
Schreiter Lab / Publications
custom | custom

Filter

facetapi-Q2b17qCsTdECvJIqZJgYMaGsr8vANl1n | block
facetapi-PV5lg7xuz68EAY8eakJzrcmwtdGEnxR0 | block
facetapi-021SKYQnqXW6ODq5W5dPAFEDBaEJubhN | block
general_search_page-panel_pane_1 | views_panes

1 Publications

Showing 1-1 of 1 results
Your Criteria:
    07/01/10 | The heparin-binding domain of HB-EGF mediates localization to sites of cell-cell contact and prevents HB-EGF proteolytic release.
    Prince RN, Schreiter ER, Zou P, Wiley HS, Ting AY, Lee RT, Lauffenburger DA
    Journal of Cell Science. 2010 Jul 1;123(Pt 13):2308-18. doi: 10.1242/jcs.058321

    Heparin-binding EGF-like growth factor (HB-EGF) is a ligand for EGF receptor (EGFR) and possesses the ability to signal in juxtacrine, autocrine and/or paracrine mode, with these alternatives being governed by the degree of proteolytic release of the ligand. Although the spatial range of diffusion of released HB-EGF is restricted by binding heparan-sulfate proteoglycans (HSPGs) in the extracellular matrix and/or cellular glycocalyx, ascertaining mechanisms governing non-released HB-EGF localization is also important for understanding its effects. We have employed a new method for independently tracking the localization of the extracellular EGF-like domain of HB-EGF and the cytoplasmic C-terminus. A striking observation was the absence of the HB-EGF transmembrane pro-form from the leading edge of COS-7 cells in a wound-closure assay; instead, this protein localized in regions of cell-cell contact. A battery of detailed experiments found that this localization derives from a trans interaction between extracellular HSPGs and the HB-EGF heparin-binding domain, and that disruption of this interaction leads to increased release of soluble ligand and a switch in cell phenotype from juxtacrine-induced growth inhibition to autocrine-induced proliferation. Our results indicate that extracellular HSPGs serve to sequester the transmembrane pro-form of HB-EGF at the point of cell-cell contact, and that this plays a role in governing the balance between juxtacrine versus autocrine and paracrine signaling.

    View Publication Page