The oligodendrocyte precursor mitogen PDGF stimulates proliferation by activation of αvβ3 integrins
The oligodendrocyte precursor mitogen PDGF stimulates proliferation by activation of αvβ3 integrins
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DOI：
10.1093/emboj/21.8.1957
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发表时间：
2002-04-15
期刊：
影响因子：
11.4
通讯作者：
ffrench-Constant, C
中科院分区：
文献类型：
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作者：
Baron, W;Shattil, SJ;ffrench-Constant, C
中枢神经系统的发育需要神经前体行为的精确和局部调节。在这里，我们展示了生长因子和整合素信号通路之间的相互作用如何为少突胶质细胞祖细胞（OP）增殖的精确性提供机制。虽然生理浓度的血小板衍生生长因子（PDGF）本身不足以促进OP增殖，但它们在结合α v β 3整联蛋白的细胞外基质（ECM）底物上可以促进OP增殖。在PDGF-AA暴露和α v β 3接合后，证明了两种受体之间的物理共缔合，证实了这些信号传导途径之间的相互作用。此外，我们发现，PDGFalphaR刺激蛋白激酶C依赖性激活整合素α v β 3，这反过来又诱导OP增殖通过磷脂酰肌醇3-激酶依赖性信号通路。这些研究建立了OP增殖依赖于ECM配体和促有丝分裂生长因子两者的可用性的机制。生长因子介导的整合素激活是增殖信号传导中的关键整合步骤，并确保神经前体细胞对长程信号的反应可以由其细胞邻居调节，从而精确控制发育期间的细胞行为。
Central nervous system development requires precise and localized regulation of neural precursor behaviour. Here we show how the interaction between growth factor and integrin signalling pathways provides a mechanism for such precision in oligodendrocyte progenitor (OP) proliferation. While physiological concentrations of platelet-derived growth factor (PDGF) were not in themselves sufficient to promote OP proliferation, they did so on extracellular matrix (ECM) substrates that bind alphavbeta3 integrin. Upon PDGF-AA exposure and alphavbeta3 engagement, a physical co-association between both receptors was demonstrated, confirming the interaction between these signalling pathways. Furthermore, we found that PDGFalphaR stimulated a protein kinase C-dependent activation of integrin alphavbeta3, which in turn induced OP proliferation via a phosphatidylinositol 3-kinase-dependent signalling pathway. These studies establish a mechanism by which OP proliferation is dependent on the availability of both an ECM ligand and a mitogenic growth factor. Growth factor-mediated integrin activation is the critical integrative step in proliferation signalling, and ensures that the response of neural precursor cells to long-range cues can be regulated by their cellular neighbours, allowing precise control of cell behaviour during development.