Brennan H, Smith S, Stoker A
Department of Biological Sciences, University of Warwick, Coventry, United Kingdom.
Cell Motil Cytoskeleton. 1999;42(2):101-13. doi: 10.1002/(SICI)1097-0169(1999)42:2<101::AID-CM2>3.0.CO;2-W.
We demonstrate that neural crest cell-cell adhesion, cell-substrate adhesion, and ultimately cell motility, are highly dependent on the balanced action of tyrosine kinases and tyrosine phosphatases. Neural crest cell migration on fibronectin is diminished in the presence of the tyrosine phosphatase inhibitor vanadate or tyrosine kinase inhibitor herbimycin A, while cadherin-rich cell-cell adhesions are significantly increased. In contrast, cells treated with the kinase inhibitor genistein have decreased motility, rearrange rapidly and reversibly into a pavement-like monolayer, but have no increase in cadherin interactions. Genistein-sensitive tyrosine kinases may therefore abrogate a latent sensitivity of neural crest cells to contact-mediated inhibition of movement. Furthermore, we show that the activity of herbimycin A-sensitive kinases is necessary for focal adhesion formation in these cells. Moreover, the size and distribution of these adhesions are acutely sensitive to the actions of tyrosine phosphatases and genistein-sensitive kinases. We propose that in migrating neural crest cells there is a balance in phosphotyrosine signalling which minimises both cell-cell adhesion and contact inhibition of movement, while enhancing dynamic cell-substrate interactions and thus the conditions for motility.
我们证明，神经嵴细胞间黏附、细胞与底物的黏附以及最终的细胞运动性，高度依赖于酪氨酸激酶和酪氨酸磷酸酶的平衡作用。在酪氨酸磷酸酶抑制剂钒酸盐或酪氨酸激酶抑制剂赫曲霉素A存在的情况下，神经嵴细胞在纤连蛋白上的迁移会减少，而富含钙黏蛋白的细胞间黏附会显著增加。相反，用激酶抑制剂染料木黄酮处理的细胞运动性降低，会迅速且可逆地重排成铺路石样的单层，但钙黏蛋白相互作用没有增加。因此，对染料木黄酮敏感的酪氨酸激酶可能消除了神经嵴细胞对接触介导的运动抑制的潜在敏感性。此外，我们表明，对赫曲霉素A敏感的激酶的活性对于这些细胞中黏着斑的形成是必需的。而且，这些黏着斑的大小和分布对酪氨酸磷酸酶和对染料木黄酮敏感的激酶的作用极为敏感。我们提出，在迁移的神经嵴细胞中，磷酸酪氨酸信号存在一种平衡，这种平衡既能使细胞间黏附以及运动的接触抑制最小化，又能增强动态的细胞与底物相互作用，从而为运动创造条件。
