Dsg2 via Src-mediated transactivation shapes EGFR signaling towards cell adhesion.

Dsg2 via Src-mediated transactivation shapes EGFR signaling towards cell adhesion.
Cell Mol Life Sci. 2018 Jul 06;:
Authors: Ungewiß H, Rötzer V, Meir M, Fey C, Diefenbacher M, Schlegel N, Waschke J
Abstract
Rapidly renewing epithelial tissues such as the intestinal epithelium require precise tuning of intercellular adhesion and proliferation to preserve barrier integrity. Here, we provide evidence that desmoglein 2 (Dsg2), an adhesion molecule of desmosomes, controls cell adhesion and proliferation via epidermal growth factor receptor (EGFR) signaling. Dsg2 is required for EGFR localization at intercellular junctions as well as for Src-mediated EGFR activation. Src binds to EGFR and is required for localization of EGFR and Dsg2 to cell-cell contacts. EGFR is critical for cell adhesion and barrier recovery. In line with this, Dsg2-deficient enterocytes display impaired barrier properties and increased cell proliferation. Mechanistically, Dsg2 directly interacts with EGFR and undergoes heterotypic-binding events on the surface of living enterocytes via its extracellular domain as revealed by atomic force microscopy. Thus, our study reveals a new mechanism by which Dsg2 via Src shapes EGFR function towards cell adhesion.
PMID: 29980799 [PubMed - as supplied by publisher]

Source: Cellular and Molecular Life Sciences : CMLS - July 6, 2018 Category: Cytology Authors: Ungewiß H, Rötzer V, Meir M, Fey C, Diefenbacher M, Schlegel N, Waschke J Tags: Cell Mol Life Sci Source Type: research