Activation of protein kinase C precedes alpha 5 beta 1 integrin-mediated cell spreading on fibronectin.
Activation of protein kinase C precedes alpha 5 beta 1 integrin-mediated cell spreading on fibronectin.
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发表时间：
1993-10
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通讯作者：
K. Vuori;E. Ruoslahti
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作者：
K. Vuori;E. Ruoslahti
越来越多的证据表明，细胞粘附受体整合素家族可以将细胞外基质的生化信号传递到细胞内部，从而调节细胞行为。我们研究了蛋白激酶C在中国仓鼠卵巢细胞α 5 β 1整合素介导的信号转导中的作用。研究发现，phphobol酯上调蛋白激酶C活性可增强细胞在纤维连接蛋白底物上的粘附、扩散和迁移，而不影响细胞表面表达或α 5 β 1整合素的纤维连接蛋白结合，而calphostin C抑制蛋白激酶C活性也会在未受刺激的细胞中抑制这些功能。此外，我们观察到细胞膜部分的蛋白激酶C活性在细胞在纤维连接蛋白上扩散之前短暂增加，但在聚赖氨酸上没有，这进一步表明蛋白激酶C在α 5 β 1整合素介导的纤维连接蛋白上的扩散中起特殊作用。用phorbol酯和calphostin C进行的实验也表明，蛋白激酶C的活性对于在纤维连接蛋白上镀的细胞中增强黏附激酶pp125fak的磷酸化是必需的。然而，没有发现蛋白激酶c - α直接作用于pp125fak，这表明这一现象涉及其他机制。
Increasing evidence indicates that the integrin family of cell adhesion receptors can transduce biochemical signals from the extracellular matrix to the cell interior to modulate cell behavior. We have investigated the role of protein kinase C in alpha 5 beta 1 integrin-mediated signal transduction in Chinese hamster ovary cells. Up-regulation of protein kinase C activity by phorbol esters was found to enhance cell adhesion, spreading, and migration on a fibronectin substrate, without affecting the cell surface expression or fibronectin binding of the alpha 5 beta 1 integrin, whereas inhibition of protein kinase C activity by calphostin C inhibited these functions as well in unstimulated cells. In addition, we observed that protein kinase C activity in the cell membrane fraction transiently increases preceding cell spreading on fibronectin, but not on polylysine, additionally implying a specific role of protein kinase C in alpha 5 beta 1 integrin-mediated spreading on fibronectin. Experiments with phorbol esters and calphostin C also suggested that protein kinase C activity is required for enhanced phosphorylation of the focal adhesion kinase, pp125fak, in cells plated on fibronectin. Protein kinase C-alpha was not, however, found to directly act on pp125fak, suggesting that other mechanisms are involved in this phenomenon.