标题：β-Arrestin 1 down-regulation after insulin treatment is associated with supersensitization of β2 adrenergic receptor Gαs signaling in 3T3-L1 adipocytes
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：1
页码：161-166
DOI：10.1073/pnas.0235674100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：{beta}-Arrestin 1 is required for internalization and mitogen-activated protein (MAP) kinase activation by the {beta}2 adrenergic receptor ({beta}2AR). Our previous studies have shown that chronic insulin treatment down-regulates cellular {beta}-arrestin 1 levels, leading to a marked impairment in G protein-coupled receptor and insulin-like growth factor-1 receptor-mediated MAP kinase and mitogenic signaling. In this study, we show that chronic insulin-treated, {beta}-arrestin 1depleted 3T3-L1 adipocytes display (i) increased isoproterenol-induced cAMP generation (53 {+/-} 38% at 1.5 min, 25 {+/-} 19% at 5 min, 63 {+/-} 14% at 30 min, and 59 {+/-} 2% at 60 min), a Gs-associated pathway; (ii) impaired isoproterenol-induced {beta}2AR internalization (reduced by 98 {+/-} 4%), which is required for MAP kinase signaling, a Gi-associated pathway; and (iii) increased {beta}-arrestin 1 phosphorylation at Ser-412. Taken together, these findings represent a hitherto unknown mechanism (degradation and phosphorylation of {beta}-arrestin, whereby the activation of the insulin receptor, belonging to the family of receptor tyrosine kinases, causes supersensitization of Gs-associated signaling and inhibition of Gi-associated signaling by the {beta}2AR, a prototypical G protein-coupled receptor.
