76 research outputs found
RPTPĪ± controls epithelial adherens junctions, linking E-cadherin engagement to c-Src-mediated phosphorylation of cortactin
Epithelial junctions are fundamental determinants of tissue organization, subject to regulation by tyrosine phosphorylation. Homophilic binding of E-cadherin activates tyrosine kinases, such as Src, that control junctional integrity. Protein tyrosine phosphatases (PTPs) also contribute to cadherin-based adhesion and signaling, but little is known about their specific identity or functions at epithelial junctions. Here, we report that the receptor PTP RPTPĪ± (human gene name PTPRA) is recruited to epithelial adherens junctions at the time of cell-cell contact, where it is in molecular proximity to E-cadherin. RPTPĪ± is required for appropriate cadherin-dependent adhesion and for cyst architecture in three-dimensional culture. Loss of RPTPa impairs adherens junction integrity, as manifested by defective E-cadherin accumulation and peri-junctional F-actin density. These effects correlate with a role for RPTPa in cellular (c)-Src activation at sites of E-cadherin engagement. Mechanistically, RPTPĪ± is required for appropriate tyrosine phosphorylation of cortactin, a major Src substrate and a cytoskeletal actin organizer. Expression of a phosphomimetic cortactin mutant in RPTPĪ±-depleted cells partially rescues F-actin and E-cadherin accumulation at intercellular contacts. These findings indicate that RPTPa controls cadherinmediated signaling by linking homophilic E-cadherin engagement to cortactin tyrosine phosphorylation through c-Src
Verbod homogenezing dringt onterecht kerk binnen: Oneens, conversietherapie is in strijd met de rechten van de mens
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