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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >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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β-Arrestin 1 down-regulation after insulin treatment is associated with supersensitization of β2 adrenergic receptor Gαs signaling in 3T3-L1 adipocytes

机译：胰岛素治疗后β-抑制蛋白1下调与3T3-L1脂肪细胞中β2肾上腺素能受体Gαs信号超敏化有关

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摘要

β-Arrestin 1 is required for internalization and mitogen-activated protein (MAP) kinase activation by the β2 adrenergic receptor (β2AR). Our previous studies have shown that chronic insulin treatment down-regulates cellular β-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, β-arrestin 1depleted 3T3-L1 adipocytes display (?) 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 Gα_s-associated pathway; (ⅱ) impaired isoproterenol-induced β2AR internalization (reduced by 98 +- 4%), which is required for MAP kinase signaling, a Gα_i-associated pathway; and (ⅲ) increased β-arrestin 1 phosphorylation at Ser-412. Taken together, these findings represent a hitherto unknown mechanism (degradation and phosphorylation of β-arrestin, whereby the activation of the insulin receptor, belonging to the family of receptor tyrosine kinases, causes supersensitization of Gα_s-associated signaling and inhibition of Gα_i-associated signaling by the β2AR, a prototypical G protein-coupled receptor.
机译：β-抑制蛋白1是β2肾上腺素能受体（β2AR）内在化和丝裂原激活蛋白（MAP）激酶激活所必需的。我们以前的研究表明，慢性胰岛素治疗会下调细胞中β-arrestin1的水平，从而导致G蛋白偶联受体和胰岛素样生长因子1受体介导的MAP激酶和促有丝分裂信号明显受损。在这项研究中，我们显示了慢性胰岛素治疗的β-arrestin1耗竭的3T3-L1脂肪细胞显示（？）增加了异丙肾上腺素诱导的cAMP生成（1.5分钟时为53 +-38％，5分钟时为25 + -19％，在30分钟时为63±14％，在60分钟时为59±2％），是与Gα_s相关的途径； （ⅱ）异丙肾上腺素诱导的β2AR内在化受损（减少98±4％），这是MAP激酶信号传导所必需的，Gα_i相关途径； （ⅲ）增加了Ser-412的β-arrestin1的磷酸化。综上所述，这些发现代表了迄今未知的机制（β-arrestin的降解和磷酸化，从而属于受体酪氨酸激酶家族的胰岛素受体的激活导致Gα_s相关信号的超敏化和Gα_i相关信号的抑制。 β2AR是典型的G蛋白偶联受体。

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