Coxsackie adenovirus receptor (CAR) regulates integrin function through activation of p44/42 MAPK |
| |
Authors: | Charlotte Farmer Marjolein Snippe Maddy Parsons |
| |
Institution: | a Division of Asthma, Allergy and Lung Biology, King's College London School of Medicine, 5th Floor Tower Wing, Guy's Hospital Campus, London SE1 9RT, UK b Randall Division of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guys Campus, London SE1 1UL, UK |
| |
Abstract: | The coxsackie B virus and adenovirus receptor (CAR) is an attachment receptor for Adenovirus serotype 5 (Ad5) and in many cell types forms homodimers with neighbouring cells as part of a cell adhesion complex. CAR co-operates with cell surface integrin receptors to enable efficient viral entry, but little is known about the mechanism of crosstalk between these two receptor types. Here we show that overexpression of CAR in human epithelial cells leads to increased basal activation of p44/42 MAPK and this is required for efficient Ad5 infection. We demonstrate that CAR forms homodimers in cis and that this dimerisation is enhanced in the presence of Ad5 in a phospho-p44/42-dependent manner. CAR-induced p44/42 activation also leads to increased activation of β1 and β3 integrins. Analysis of CAR mutants demonstrates that the cyto domain of CAR is required for CAR-induced p44/42 activation, integrin activation and localisation to cell junctions. This data for the first time demonstrates that signalling downstream of CAR can have a dual effect on integrins and CAR itself in order to promote efficient viral binding to cell membranes. |
| |
Keywords: | CAR Adenovirus P44/42 Integrin Adhesion |
本文献已被 ScienceDirect 等数据库收录! |
|