β-Arrestin–Dependent Endocytosis of Proteinase-Activated Receptor 2 Is Required for Intracellular Targeting of Activated Erk1/2

Recently, a requirement for β-arrestin–mediated endocytosis in the activation of extracellular signal–regulated kinases 1 and 2 (ERK1/2) by several G protein–coupled receptors (GPCRs) has been proposed. However, the importance of this requirement for function of ERK1/2 is unknown. We report that agonists of Gαq-coupled proteinase–activated receptor 2 (PAR2) stimulate formation of a multiprotein signaling complex, as detected by gel filtration, immunoprecipitation and immunofluorescence. The complex, which contains internalized receptor, β-arrestin, raf-1, and activated ERK, is required for ERK1/2 activation. However, ERK1/2 activity is retained in the cytosol and neither translocates to the nucleus nor causes proliferation. In contrast, a mutant PAR2 (PAR2δST363/6A), which is unable to interact with β-arrestin and, thus, does not desensitize or internalize, activates ERK1/2 by a distinct pathway, and fails to promote both complex formation and cytosolic retention of the activated ERK1/2. Whereas wild-type PAR2 activates ERK1/2 by a PKC-dependent and probably a ras-independent pathway, PAR2(δST363/6A) appears to activate ERK1/2 by a ras-dependent pathway, resulting in increased cell proliferation. Thus, formation of a signaling complex comprising PAR2, β-arrestin, raf-1, and activated ERK1/2 might ensure appropriate subcellular localization of PAR2-mediated ERK activity, and thereby determine the mitogenic potential of receptor agonists

Application Composition Driven by UI Composition

International audienceAhead of the multiplication of specialized applications, needs for application composition increase. Each application can be described by a pair of a visible part –the User Interface (UI) –and a hidden part –the tasks and the Functional Core (FC). Few works address the problem of application composition by handling both visible and hidden parts at the same time. Our proposition described in this paper is to start from the visible parts of applications, their UIs, to build a new application while using information coming from UIs as well as from tasks. We base upon the semantic description of UIs to help the developer merge parts of former applications. We argue that this approach driven by the composition of UIs helps the user during the composition process and ensures the preservation of a usable UI for the resulting application