The chemotactic response to PDGF-BB: evidence of a role for Ras.
The chemotactic response to PDGF-BB: evidence of a role for Ras.
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DOI：
10.1083/jcb.130.3.725
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发表时间：
1995-08
期刊：
影响因子：
--
通讯作者：
Zetter BR
中科院分区：
文献类型：
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作者：
Kundra V;Anand-Apte B;Feig LA;Zetter BR
PDGF受体-β介导对PDGF-BB的促有丝分裂和趋化反应。尽管Ras在酪氨酸激酶介导的有丝分裂发生中的作用已被广泛表征，但其在PDGF刺激的趋化性中的作用尚未确定。使用表达显性负性ras的细胞，我们发现Ras抑制抑制向PDGF-BB的迁移。Ras-GT3激活蛋白（Ras-GAP）或Ras鸟嘌呤释放因子（GRF）的过表达也抑制PDGF刺激的趋化性。此外，产生过量组成型活性Ras的细胞不能向PDGF-BB迁移，这与过量配体或过量信号传导中间体可以抑制趋化反应的观察结果一致。这些结果表明，Ras可以在正常细胞中发挥作用，以支持对PDGF-BB的趋化性，并且太少或太多的Ras活性可以消除趋化反应。与Ras过表达相反，产生过量组成型活性Raf（Ras的下游效应子）的细胞确实向PDGF-BB迁移。表达显性阴性Ras的细胞能够向可溶性纤连蛋白迁移，表明这些细胞保留了迁移的能力。这些结果表明Ras是PDGF刺激的趋化性的中间体，但可能不是纤连蛋白刺激的细胞运动所必需的。
The PDGF receptor-beta mediates both mitogenic and chemotactic responses to PDGF-BB. Although the role of Ras in tyrosine kinase- mediated mitogenesis has been characterized extensively, its role in PDGF-stimulated chemotaxis has not been defined. Using cells expressing a dominant-negative ras, we find that Ras inhibition suppresses migration toward PDGF-BB. Overexpression of either Ras-GTPase activating protein (Ras-GAP) or a Ras guanine releasing factor (GRF) also inhibited PDGF-stimulated chemotaxis. In addition, cells producing excess constitutively active Ras failed to migrate toward PDGF-BB, consistent with the observation that either excess ligand or excess signaling intermediate can suppress the chemotactic response. These results suggest that Ras can function in normal cells to support chemotaxis toward PDGF-BB and that either too little or too much Ras activity can abrogate the chemotactic response. In contrast to Ras overexpression, cells producing excess constitutively active Raf, a downstream effector of Ras, did migrate toward PDGF-BB. Cells expressing dominant-negative Ras were able to migrate toward soluble fibronectin demonstrating that these cells retained the ability to migrate. These results suggest that Ras is an intermediate in PDGF- stimulated chemotaxis but may not be required for fibronectin- stimulated cell motility.