Parallel phosphatidylinositol-3 kinase and p42/44 mitogen-activated protein kinase signaling pathways subserve the mitogenic and antiapoptotic actions of insulin-like growth factor I in osteoblastic cells
Parallel phosphatidylinositol-3 kinase and p42/44 mitogen-activated protein kinase signaling pathways subserve the mitogenic and antiapoptotic actions of insulin-like growth factor I in osteoblastic cells
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DOI：
10.1210/en.2003-0350
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发表时间：
2003-11-01
期刊：
影响因子：
4.8
通讯作者：
Cornish, J
中科院分区：
文献类型：
--
作者：
Grey, A;Chen, Q;Cornish, J
IGF-I是骨骼稳态的内分泌和旁分泌调节剂，主要通过其对成骨细胞的合成代谢作用。在目前的研究中，我们研究了IGF-I促进SaOS-2人成骨细胞增殖和存活的细胞内信号通路。抑制磷脂酰肌醇-3激酶（PI-3激酶）、p42/44 MAPK和p70 s6激酶途径中的每一种都部分抑制了IGF-I刺激成骨细胞增殖和存活的能力。因为在用IGF-I处理的成骨细胞中，p70 s6激酶的活化是PI-3激酶和p42/44 MAPK活化的下游，所以该核糖体激酶代表成骨细胞中IGF-I诱导的PI-3激酶和p42/44 MAPK信号传导的汇聚点。此外，PI-3激酶依赖性Akt信号传导的取消，不抑制IGF-I诱导的p70 s6激酶磷酸化，也抑制了IGF-I在成骨细胞中的抗凋亡作用。最后，G（β-γ）信号的中断部分地消除了IGF-I促进成骨细胞存活的能力，而不抑制通过PI-3激酶/Akt、p42/44 MAPK或p70 s6激酶的信号。这些数据表明，IGF-I信号成骨细胞有丝分裂和生存通过平行的，部分重叠的细胞内途径，涉及PI-3激酶，p42/44 MAPK，和G（β-γ）亚基。
IGF-I is an endocrine and paracrine regulator of skeletal homeostasis, principally by virtue of its anabolic effects on osteoblastic cells. In the current study, we examined the intracellular signaling pathways by which IGF-I promotes proliferation and survival in SaOS-2 human osteoblastic cells. Inhibition of each of the phosphatidylinositol-3 kinase (PI-3 kinase), p42/44 MAPK, and p70s6 kinase pathways partially inhibited the ability of IGF-I to stimulate osteoblast proliferation and survival. Because activation of p70s6 kinase is downstream of both PI-3 kinase and p42/44 MAPK activation in osteoblasts treated with IGF-I, this ribosomal kinase represents a convergence point for IGF-I-induced PI-3 kinase and p42/44 MAPK signaling in osteoblastic cells. In addition, abrogation of PI-3 kinase-dependent Akt signaling, which does not inhibit IGF-I-induced p70s6 kinase phosphorylation, also inhibited the antiapoptotic effects of IGF-I in osteoblasts. Finally, interruption of G(betagamma) signaling partially abrogated the ability of IGF-I to promote osteoblast survival, without inhibiting signaling through PI-3 kinase/Akt, p42/44 MAPKs, or p70s6 kinase. These data suggest that IGF-I signals osteoblast mitogenesis and survival through parallel, partly overlapping intracellular pathways involving PI-3 kinase, p42/44 MAPKs, and G(betagamma) subunits.