Differential effects of beta-arrestins on internalization, desensitization and ERK1/2 activation downstream of Protease Activated Receptor-2. Export

@article{citeulike:1244594, abstract = {beta-arrestins-1 and 2 are known to play important roles in desensitization of membrane receptors and facilitation of signal transduction pathways. It has been previously shown that beta-arrestins are required for signal termination, internalization and ERK1/2 activation downstream of Protease-activated-receptor-2 (PAR-2), but it is unclear whether they are functionally redundant or mediate specific events. Here we demonstrate that in MEFs from beta-arrestin-1/2 knockout mice, Galphaq signaling by PAR-2, as measured by mobilization of intracellular Ca(2+), is prolonged. Only expression of beta-arrestin-1 shortened the signal duration, whereas either beta-arrestin-1 or 2 was able to restore Protein Kinase C-induced receptor desensitization. beta-arrestin-1 also mediated early, while beta-arrestin-2 mediated delayed, receptor internalization and membrane-associated ERK1/2 activation. While beta-arrestin-1 colocalized with a lysosomal marker (LAMP-1), beta-arrestin-2 did not, suggesting a specific role for beta-arrestin-1 in lysosomal receptor degradation. Together these data suggest distinct temporal and functional roles for beta-arrestins in PAR-2 signaling, desensitization and internalization. Key words: arrestins, PAR-2, protease-activated-receptor, G-protein-coupled receptor, ERK1/2.}, address = {Biomedica Sciences, UC Riverside, Riverside, California, United States.}, author = {Kumar, Puneet and Lau, Chang and Wang, Ping and Mathur, Maneesh and Defea, Kathryn Anne A.}, citeulike-article-id = {1244594}, citeulike-linkout-0 = {http://dx.doi.org/10.1152/ajpcell.00010.2007}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/17442737}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=17442737}, day = {18}, doi = {10.1152/ajpcell.00010.2007}, issn = {0363-6143}, journal = {Am J Physiol Cell Physiol}, keywords = {arrestin, gprcr, trafficking}, month = {April}, posted-at = {2007-04-23 09:33:33}, priority = {2}, title = {Differential effects of {beta}-arrestins on internalization, desensitization and ERK1/2 activation downstream of Protease Activated Receptor-2.}, url = {http://dx.doi.org/10.1152/ajpcell.00010.2007}, year = {2007} }

TY - JOUR ID - citeulike:1244594 L3 - citeulike-article-id:1244594 N2 - beta-arrestins-1 and 2 are known to play important roles in desensitization of membrane receptors and facilitation of signal transduction pathways. It has been previously shown that beta-arrestins are required for signal termination, internalization and ERK1/2 activation downstream of Protease-activated-receptor-2 (PAR-2), but it is unclear whether they are functionally redundant or mediate specific events. Here we demonstrate that in MEFs from beta-arrestin-1/2 knockout mice, Galphaq signaling by PAR-2, as measured by mobilization of intracellular Ca(2+), is prolonged. Only expression of beta-arrestin-1 shortened the signal duration, whereas either beta-arrestin-1 or 2 was able to restore Protein Kinase C-induced receptor desensitization. beta-arrestin-1 also mediated early, while beta-arrestin-2 mediated delayed, receptor internalization and membrane-associated ERK1/2 activation. While beta-arrestin-1 colocalized with a lysosomal marker (LAMP-1), beta-arrestin-2 did not, suggesting a specific role for beta-arrestin-1 in lysosomal receptor degradation. Together these data suggest distinct temporal and functional roles for beta-arrestins in PAR-2 signaling, desensitization and internalization. Key words: arrestins, PAR-2, protease-activated-receptor, G-protein-coupled receptor, ERK1/2. JF - Am J Physiol Cell Physiol SN - 0363-6143 AD - Biomedica Sciences, UC Riverside, Riverside, California, United States. TI - Differential effects of {beta}-arrestins on internalization, desensitization and ERK1/2 activation downstream of Protease Activated Receptor-2. KW - arrestin KW - gprcr KW - trafficking AU - Kumar, Puneet AU - Lau, Chang AU - Wang, Ping AU - Mathur, Maneesh AU - Defea, Kathryn Anne PY - 2007/04/18/ UR - http://dx.doi.org/10.1152/ajpcell.00010.2007 ER -