GTPases and phosphatidylinositol 3-kinase are critical for insulin-like growth factor-I-mediated Schwann cell motility.
GTPases and phosphatidylinositol 3-kinase are critical for insulin-like growth factor-I-mediated Schwann cell motility.
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DOI：
10.1074/jbc.m002534200
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发表时间：
2000-09
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影响因子：
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通讯作者：
Hsin‐Lin Cheng;Matthew L. Steinway;J. Russell;Eva L. Feldman
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文献类型：
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作者：
Hsin‐Lin Cheng;Matthew L. Steinway;J. Russell;Eva L. Feldman
以前，我们报道胰岛素样生长因子-I（IGF-I）促进神经细胞的运动和粘着斑激酶（FAK）激活。在目前的研究中，我们研究了IGF-I在雪旺细胞（SC）运动中的作用。IGF-I增加SC过程延伸和运动性。同时，IGF-I激活IGF-I受体、胰岛素受体底物-1（IRS-1）、磷脂酰肌醇3（PI-3）-激酶和FAK。PI-3激酶抑制剂LY 294002阻断IGF-I诱导的运动和FAK磷酸化。GTP酶的Rho家族在细胞骨架的调节中是重要的。组成型活性Leu-61 Cdc 42和瓦尔-12 Rac 1的过表达增强SC运动性，这不受LY 294002的影响。与此同时，用显性负性Asn-17 Rac 1稳定转染SC可阻断IGF-I介导的SC运动性和FAK磷酸化，这意味着Rac是FAK的上游调节因子。总的来说，我们的研究结果表明，IGF-I调节SC运动的重组肌动蛋白细胞骨架通过下游激活PI-3激酶，小GT3，FAK途径。
Previously, we reported insulin-like growth factor-I (IGF-I) promotes motility and focal adhesion kinase (FAK) activation in neuronal cells. In the current study, we examined the role of IGF-I in Schwann cell (SC) motility. IGF-I increases SC process extension and motility. In parallel, IGF-I activates IGF-I receptor, insulin receptor substrate-1 (IRS-1), phosphatidylinositol 3 (PI-3)-kinase, and FAK. LY294002, a PI-3 kinase inhibitor, blocks IGF-I-induced motility and FAK phosphorylation. The Rho family of GTPases is important in the regulation of the cytoskeleton. Overexpression of constitutively active Leu-61 Cdc42 and Val-12 Rac1 enhances SC motility which is unaffected by LY294002. In parallel, stable transfection of SC with dominant negative Asn-17 Rac1 blocks IGF-I-mediated SC motility and FAK phosphorylation, implying Rac is an upstream regulator of FAK. Collectively our results suggest that IGF-I regulates SC motility by reorganization of the actin cytoskeleton via the downstream activation of a PI-3 kinase, small GTPase, and FAK pathway.