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Wei H., Ahn S., Shenoy S.K., Karnik S.S., Hunyady L., Luttrell L.M., Lefkowitz R.J. Independent β-arrestin2 and G-protein-mediated pathways for angiotensin II activation of extracellular signal-regulated kinases 1 and 2. Proc. Natl. Acad. Sci. U S A. 100:2003;10782-10787 These studies are the first to demonstrate 7MSR-stimulated β-arresin-2-mediated Erk activation, completely independent of heterotrimeric G-protein activation.
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Azzi M, Charest PG, Angers S, Rousseau G, Kohout T, Bouvier M, Pineyro G: β-arrestin-mediated activation of MAPK by inverse agonists reveals distinct active conformations for G-protein-coupled receptors. Proc Natl Acad Sci U S A 2003, in press.
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Povsic T, Kohout TA, Lefkowitz RJ: β-arrestin1 mediates IGF-1 activation of PI-3-K and anti-apoptosis. J Biol Chem 2003, in press.
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J Biol Chem
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Povsic, T.1
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Dalle S., Imamura T., Rose D.W., Worrall D.S., Ugi S., Hupfeld C.J., Olefsky J.M. Insulin induces heterologous desensitization of G-protein-coupled receptor and insulin-like growth factor I signaling by downregulating β-arrestin1. Mol. Cell. Biol. 22:2002;6272-6285
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β-arrestin 1 down-regulation after insulin treatment is associated with supersensitization of β2 adrenergic receptor Gαs signaling in 3T3-L1 adipocytes
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2AR-stimulated cAMP generation. These studies reveal a mechanism by which insulin receptor stimulation can regulate 7MSR function/regulation by affecting β-arrestin1-mediated receptor desensitization and internalization.
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Fong A.M., Premont R.T., Richardson R.M., Yu Y.R., Lefkowitz R.J., Patel D.D. Defective lymphocyte chemotaxis in β-arrestin2- and GRK6-deficient mice. Proc. Natl. Acad. Sci. U S A. 99:2002;7478-7483 Differential regulation and signaling involved in the complex processes driving CXCL12 chemotaxis by different GRKs and β-arrestin2. These studies demonstrate a cell-type-specific chemotactic defect and a positive regulatory role for GRK6 and β-arrestin2 in mediating the chemotactic responses of T and B lymphocytes.
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Fong, A.M.1
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Walker J, Fong A, Lawson B, Savov J, Patel D, Schwartz D, Lefkowitz R: β-arrestin2 regulates the development of allergic asthma. J Clin Invest 2003, in press.
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A β-arrestin-dependent scaffold is associated with prolonged MAPK activation in pseudopodia during protease-activated receptor-2-induced chemotaxis
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Ge L., Ly Y., Hollenberg M., DeFea K. A β-arrestin-dependent scaffold is associated with prolonged MAPK activation in pseudopodia during protease-activated receptor-2-induced chemotaxis. J. Biol. Chem. 278:2003;34418-34426 The authors demonstrate increased β-arrestin- associated phospho-ERK1/2 in pseudopodia during PAR2-induced chemotaxis, suggesting a physiological role for β-arrestin-mediated scaffolding in chemotaxis.
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β-arrestins regulate a Ral-GDS Ral effector pathway that mediates cytoskeletal reorganization
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Bhattacharya M., Anborgh P.H., Babwah A.V., Dale L.B., Dobransky T., Benovic J.L., Feldman R.D., Verdi J.M., Rylett R.J., Ferguson S.S. β-arrestins regulate a Ral-GDS Ral effector pathway that mediates cytoskeletal reorganization. Nat. Cell. Biol. 4:2002;547-555 β-arrestins bind inactive Ral-GDS in the cytosol. fMLP-receptor stimulation leads to the dissociation of this complex and translocation of active Ral-GDS and β-arrestin to the plasma membrane. Re-association of this complex leads to Ral-GDS inactivation. These studies demonstrate 7MSR-mediated regulation of the Ras GTPase, Ral, by β-arrestin.
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Bhattacharya, M.1
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