Ilić D, Furuta Y, Kanazawa S, Takeda N, Sobue K, Nakatsuji N, Nomura S, Fujimoto J, Okada M, Yamamoto T
Department of Morphogenesis, Kumamoto University School of Medicine, Japan.
Nature. 1995 Oct 12;377(6549):539-44. doi: 10.1038/377539a0.
The intracellular protein tyrosine kinase FAK (focal adhesion kinase) was originally identified gy its high level of tyrosine phosphorylation in v-src-transformed cells. FAK is also highly phosphorylated during early development. In cultured cells it is localized to focal adhesion contacts and becomes phosphorylated and activated in response to integrin-mediated binding of cells to the extracellular matrix, suggesting an important role in cell adhesion and/or migration. We have generated FAK-deficient mice by gene targeting to examine the role of FAK during development. Mutant embryos displayed a general defect of mesoderm development, and cells from these embryos had reduced mobility in vitro. Surprisingly, the number of focal adhesions was increased in FAK-deficient cells, suggesting that FAK may be involved in the turnover of focal adhesion contacts during cell migration.
细胞内蛋白酪氨酸激酶FAK（粘着斑激酶）最初是因其在v-src转化细胞中高水平的酪氨酸磷酸化而被鉴定出来的。FAK在早期发育过程中也高度磷酸化。在培养细胞中，它定位于粘着斑，并且在整合素介导的细胞与细胞外基质结合时发生磷酸化并被激活，这表明其在细胞粘附和/或迁移中起重要作用。我们通过基因打靶产生了FAK缺陷小鼠，以研究FAK在发育过程中的作用。突变胚胎表现出中胚层发育的普遍缺陷，并且来自这些胚胎的细胞在体外的迁移能力降低。令人惊讶的是，FAK缺陷细胞中的粘着斑数量增加，这表明FAK可能参与细胞迁移过程中粘着斑的周转。
