Insulin and insulin-like growth factor I receptors utilize different G protein signaling components
Insulin and insulin-like growth factor I receptors utilize different G protein signaling components
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DOI：
10.1074/jbc.m010884200
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发表时间：
2001-05-11
影响因子：
4.8
通讯作者：
Olefsky, JM
中科院分区：
文献类型：
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作者：
Dalle, S;Ricketts, W;Olefsky, JM
我们研究了异三聚体 G 蛋白信号传导成分在胰岛素和胰岛素样生长因子 I (IGF-I) 作用中的作用。在 HIRcB 细胞和 3T3L1 脂肪细胞中，用 G α (i) 抑制剂（百日咳毒素）处理或显微注射 G β γ 抑制剂（谷胱甘肽 S-转移酶-β ARK）可抑制 IGF-I 和溶血磷脂酸刺激的有丝分裂，但对表皮生长因子 (EGF) 或 胰岛素作用。在基础状态下，G α (i) 和 G β 与 IGF-I 受体 (IGF-IR) 相关，配体刺激后，IGF-IR 与 G α (1) 的关联增加，同时 G β 关联减少。未发现 Ga-i 与胰岛素或 EGF 受体相关。显微注射抗β-arrestin-1抗体特异性抑制IGF-I促有丝分裂作用，但对EGF或胰岛素作用没有影响。 beta-Arrestin-1 以配体依赖性方式与 IGF-I、胰岛素和 EGF 受体相关。我们证明 G α (i)、β γ 亚基和 β -arrestin-1 在 IGF-I 有丝分裂信号传导中均发挥着关键作用。相比之下，代谢（例如 GLUT4 易位）和胰岛素的有丝分裂信号传导都不依赖于这些蛋白质成分。这些结果表明胰岛素受体和 IGF-IR 可以作为 G 蛋白偶联受体发挥作用，并与不同的 G 蛋白伴侣结合进行下游信号传导。
We examined the role of heterotrimeric G protein signaling components in insulin and insulin-like growth factor I (IGF-I) action. In HIRcB cells and in 3T3L1 adipocytes, treatment with the G alpha (i) inhibitor (pertussis toxin) or microinjection of the G beta gamma inhibitor (glutathione S-transferase-beta ARK) inhibited IGF-I and lysophosphatidic acid-stimulated mitogenesis but had no effect on epidermal growth factor (EGF) or insulin action. In basal state, G alpha (i) and G beta were associated with the IGF-I receptor (IGF-IR), and after ligand stimulation the association of IGF-IR with G alpha (1) increased concomitantly with a decrease in G beta association. No association of Ga-i was found with either the insulin or EGF receptor. Microinjection of anti-beta -arrestin-1 antibody specifically inhibited IGF-I mitogenic action but had no effect on EGF or insulin action. beta -Arrestin-1 was associated with the receptors for IGF-I, insulin, and EGF in a ligand-dependent manner. We demonstrated that G alpha (i), beta gamma subunits, and beta -arrestin-1 all play a critical role in IGF-I mitogenic signaling. In contrast, neither metabolic, such as GLUT4 translocation, nor mitogenic signaling by insulin is dependent on these protein components. These results suggest that insulin receptors and IGF-IRs can function as G protein-coupled receptors and engage different G protein partners for downstream signaling.