Arrestin serves as a molecular switch, linking endogenous alpha 2-adrenergic receptor to SRC-dependent but not SRC-independent ERK activation. Export

@article{citeulike:802108, abstract = {Our previous studies have demonstrated that neither receptor endocytosis nor arrestin is required for ERK activation by the alpha(2)-adrenergic receptor (Wang et. al., Science (2004) 304: 1940). The present studies address whether arrestin plays a role in determining the route of alpha(2)AR-evoked ERK signaling activation, taking advantage of endogenous expression of the alpha(2A)AR subtype in mouse embryonic fibroblasts and the availability of MEFs without arrestin expression (derived from Arr2,3(-/-) mice). Our data demonstrate that the endogenous alpha(2A)AR evokes ERK phosphorylation through both a Src-dependent and Src-independent pathway, both of which are G protein-dependent and converge on the Ras-Raf-MEK pathway. Arrestin is essential to recruit Src to this process, as alpha(2A)AR-mediated ERK signaling in Arr2,3(-/-) MEFs does not involve Src. Stimulation of alpha(2A)AR enhances arrestin-Src interaction and promotes activation of Src. Alpha2-agonists have similar potencies in stimulating Src-dependent and Src-independent ERK phosphorylation in WT and Arr2,3(-/-) cells, respectively. However, Src-independent alpha(2A)AR-mediated ERK stimulation has both a longer duration of activation and a more rapid translocation of pERK into the nucleus when compared to Src-dependent activation. These data not only affirm the role of arrestin as an escort for signaling molecules such as Src family kinases, but also demonstrate the impact of arrestin-dependent modulation on both the temporal and spatial properties of ERK activation.}, address = {Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, AL 35294.}, author = {Wang, Qin and Lu, Roujian and Zhao, Jiali and Limbird, Lee E E.}, citeulike-article-id = {802108}, citeulike-linkout-0 = {http://dx.doi.org/10.1074/jbc.M605415200}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/16809338}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=16809338}, day = {29}, doi = {10.1074/jbc.M605415200}, issn = {0021-9258}, journal = {J Biol Chem}, keywords = {arrestin-1, mir, src}, month = {June}, posted-at = {2006-08-15 15:16:49}, priority = {2}, title = {Arrestin serves as a molecular switch, linking endogenous alpha 2-adrenergic receptor to SRC-dependent but not SRC-independent ERK activation.}, url = {http://dx.doi.org/10.1074/jbc.M605415200}, year = {2006} }

TY - JOUR ID - citeulike:802108 L3 - citeulike-article-id:802108 N2 - Our previous studies have demonstrated that neither receptor endocytosis nor arrestin is required for ERK activation by the alpha(2)-adrenergic receptor (Wang et. al., Science (2004) 304: 1940). The present studies address whether arrestin plays a role in determining the route of alpha(2)AR-evoked ERK signaling activation, taking advantage of endogenous expression of the alpha(2A)AR subtype in mouse embryonic fibroblasts and the availability of MEFs without arrestin expression (derived from Arr2,3(-/-) mice). Our data demonstrate that the endogenous alpha(2A)AR evokes ERK phosphorylation through both a Src-dependent and Src-independent pathway, both of which are G protein-dependent and converge on the Ras-Raf-MEK pathway. Arrestin is essential to recruit Src to this process, as alpha(2A)AR-mediated ERK signaling in Arr2,3(-/-) MEFs does not involve Src. Stimulation of alpha(2A)AR enhances arrestin-Src interaction and promotes activation of Src. Alpha2-agonists have similar potencies in stimulating Src-dependent and Src-independent ERK phosphorylation in WT and Arr2,3(-/-) cells, respectively. However, Src-independent alpha(2A)AR-mediated ERK stimulation has both a longer duration of activation and a more rapid translocation of pERK into the nucleus when compared to Src-dependent activation. These data not only affirm the role of arrestin as an escort for signaling molecules such as Src family kinases, but also demonstrate the impact of arrestin-dependent modulation on both the temporal and spatial properties of ERK activation. JF - J Biol Chem SN - 0021-9258 AD - Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, AL 35294. TI - Arrestin serves as a molecular switch, linking endogenous alpha 2-adrenergic receptor to SRC-dependent but not SRC-independent ERK activation. KW - arrestin-1 KW - mir KW - src AU - Wang, Qin AU - Lu, Roujian AU - Zhao, Jiali AU - Limbird, Lee E PY - 2006/06/29/ UR - http://dx.doi.org/10.1074/jbc.M605415200 ER -