Evidence for the involvement of two pathways in activation of extracellular signal-regulated kinase (Erk) and cell proliferation by Gi and Gq protein-coupled receptors in osteoblast-like cells
Evidence for the involvement of two pathways in activation of extracellular signal-regulated kinase (Erk) and cell proliferation by Gi and Gq protein-coupled receptors in osteoblast-like cells
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DOI：
10.1359/jbmr.2000.15.9.1697
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发表时间：
2000-09-01
影响因子：
6.2
通讯作者：
Bonjour, JP
中科院分区：
文献类型：
--
作者：
Caverzasio, J;Palmer, G;Bonjour, JP
Gi和Gq蛋白偶联受体介导成骨细胞样细胞中促有丝分裂信号传导的机制尚不清楚，并使用特异性受体激动剂如溶血磷脂酸（LPA）和前列腺素F-2 α（PGF（2 α））在MC 3 T3-E1细胞中进行了研究。与它们在表皮生长因子（EGF）受体酪氨酸激酶信号传导中的意义相反，衔接蛋白Shc、Grb 2/Sos复合物和小G蛋白Ras不参与MC 3 T3-E1细胞中由LPA或PGF（2 α）诱导的Erk的激活，这表明Gi和Gq蛋白偶联受体对Erk的激活在这些细胞中是Ras独立的，使用特定的激酶抑制剂和动力学分析，我们提供的证据表明，两个不同的组件在激活ERK的Gi和Gq蛋白偶联受体在MC 3 T3-E1细胞，包括Src样激酶依赖性途径和蛋白激酶C（PKC）依赖性机制。功能分析表明，这两种成分是响应LPA和PGF（2 α）的最佳DNA合成所必需的。这些结果表明，在刺激Erk和细胞复制的生长因子通过Gi和Gq蛋白偶联受体在骨形成细胞中的作用的两个途径的含义。
The mechanisms by which Gi and Gq protein-coupled receptors mediate mitogenic signaling in osteoblast-like cells are unknown and were investigated in MC3T3-E1 cells using specific receptor agonists such as lysophosphatidic acid (LPA) and prostaglandin F-2 alpha (PGF(2 alpha)). In contrast to their implication in epidermal growth factor (EGF) receptor tyrosine kinase signaling, the adaptor protein Shc, the Grb2/Sos complex, and the small G protein Ras were not involved in the activation of Erk induced by either LPA or PGF(2 alpha) in MC3T3-E1 cells, suggesting that activation of Erk by Gi and Gq protein-coupled receptors is Ras independent in these cells, Using specific kinase inhibitors and kinetic analyses, we provide evidence for two distinct components in the activation of Erk by Gi and Gq protein-coupled receptors in MC3T3-E1 cells including an Src-like kinase-dependent pathway and a protein kinase C (PKC)-dependent mechanism. Functional analyses suggested that these two components are required for optimal DNA synthesis in response to LPA and PGF(2 alpha). These results suggest the implication of two pathways in the stimulation of Erk and cell replication by growth factors acting through Gi and Gq protein-coupled receptors in bone-forming cells.