Inhibition of PKA blocks fibroblast migration in response to growth factors
Inhibition of PKA blocks fibroblast migration in response to growth factors
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DOI：
10.1006/excr.2001.5345
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发表时间：
2001-11-01
影响因子：
3.7
通讯作者：
Juliano, RL
中科院分区：
文献类型：
--
作者：
Edin, ML;Howe, AK;Juliano, RL
细胞迁移需要许多信号通路的精确协调以实现定向运动。我们在这里报告，NIH 3 T3成纤维细胞表达显性负PKA亚基（dnPKA）显示减少迁移血清或生长因子。这种效应不是对细胞运动性的一般效应，而是响应刺激增强迁移的能力降低。对照（neo）和dnPKA细胞显示出非常相似的向纤连蛋白的趋触性迁移，但dnPKA细胞显示出响应于EGF/PDGF或血清的迁移刺激减少。这些影响不是由于细胞生长或粘附到纤连蛋白的改变。毛喉素，提高环磷酸腺苷（cAMP）水平，显着抑制新细胞的运动在刮迁移试验，虽然dnPKA细胞迁移不受影响。MEK选择性抑制剂U 0126和磷脂酰肌醇-3激酶（PI 3 K）抑制剂LY 294002抑制迁移的neo细胞，并能够进一步抑制残留的dnPKA细胞迁移。我们的数据表明，中间或良好控制的PKA活性水平所需的最佳生长因子刺激的成纤维细胞迁移。PKA可能在导致运动的信号传导过程中起重要作用。(C)北京：科学出版社.
Cell migration requires precise coordination of many signaling pathways to achieve directed motility. We report here that NIH3T3 fibroblasts expressing a dominant negative PKA subunit (dnPKA) show diminished migration in response to serum or growth factors. This effect is not a general effect on cell motility, but rather a decreased capacity to enhance migration in response to stimuli. Control (neo) and dnPKA cells show very similar haptotactic migration toward fibronectin, but dnPKA cells show reduced stimulation of migration in response to EGF/PDGF or serum. These effects were not due to alterations in cell growth or adhesion to fibronectin. Forskolin, which elevates cyclic adenosine monophosphate (cAMP) levels, dramatically inhibited neo cell motility in a scrape migration assay, although dnPKA cell migration was unaffected. The MEK selective inhibitor U0126 and the phosphatidyl-inositol-3 kinase (PI3K) inhibitor LY294002 inhibited migrating neo cells and were able to further inhibit residual dnPKA cell migration. Our data show that intermediate or well-controlled levels of PKA activity are required for optimal growth factor-stimulated migration in fibroblasts. PKA may play an important role in the signaling processes that lead to Motility. (C) 2001 Academic Press.