Functional analysis of FAK tyrosine kinase in intracellular signaling pathways

FAK酪氨酸激酶在细胞内信号通路中的功能分析

• 批准号: 09680668
• 负责人: FUJIMOTO Jiro
• 金额: $ 0.9万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09680668/
• 关键词: cell adhesion; tyrosine kinase; Drosophila

The FAK protein-tyrosine kinase plays important roles in cell adhesion in vertebrates. Using PCR-based cloning strategy, we cloned a Drosophila gene that was homologous to the vertebrate FAK family of protein-tyrosine kinases. We designated this gene Dfak56, and characterized its gene product. The overall protein structure and deduced amino acid sequence of Dfak56 showed significant similarity to FAK and PYK2. Dfak56 had in, vitro autophosphorylation activity on tyrosine residues. Expression of the Dfak56 mRNA and the protein was observed in the central nervous system and muscle-epidermis attachment site in the embryo, where Drosophila position-specific integrins are localized. The results suggest that like FAK in vertebrates, Dfak56 functions downstream of integrins. Dfak56 was tyrosine-phosphorylated upon integrin-dependent attachment of the cell to the extracellular matrix. We conclude that the Dfak56 tyrosine kinase is involved in integrin-mediated cell adhesion signaling and thus, is a functional homolog of vertebrate FAK.

FAK蛋白酪氨酸激酶在脊椎动物细胞粘附中起重要作用。利用基于pcr的克隆策略，我们克隆了一个与脊椎动物FAK蛋白酪氨酸激酶家族同源的果蝇基因。我们将该基因命名为Dfak56，并对其基因产物进行了表征。Dfak56的整体蛋白质结构和推导出的氨基酸序列与FAK和PYK2具有显著的相似性。Dfak56对酪氨酸残基具有体外自磷酸化活性。Dfak56 mRNA和蛋白的表达在胚胎的中枢神经系统和肌肉-表皮附着部位（果蝇位置特异性整合素定位的地方）被观察到。结果表明，与脊椎动物中的FAK一样，Dfak56在整合素的下游起作用。在细胞与细胞外基质的整合素依赖性附着过程中，Dfak56被酪氨酸磷酸化。我们得出结论，Dfak56酪氨酸激酶参与整合素介导的细胞粘附信号传导，因此是脊椎动物FAK的功能同源物。

项目成果

Fujimoto, J. et al.: "Cloning and characterization of Dfak56,a homolog of focal adhesion kinase,in Drosophila melanogaster"Journal of Biological Chemistry. 274. 29196-29201 (1999)

Fujimoto, J. 等人：“果蝇中粘着斑激酶同源物 Dfak56 的克隆和表征”生物化学杂志。

Fujimoto, J. et al.: "Cloning and characterization of Dfak56, a homolog of focal adhesion kinase, in Drosophila melanogaster"Journal of Biological Chemistry. 274. 29196-29201 (1999)

Fujimoto, J. 等人：“果蝇中粘着斑激酶同源物 Dfak56 的克隆和表征”生物化学杂志。