ROLES OF PYK2 AND FAK IN RAT CENTRAL NERVOUS SYSTEM

这项拟议研究的目标是确定 大鼠中枢神经系统粘着斑激酶(FAK)焦点 黏附蛋白激酶是一种125 kDa的胞浆蛋白酪氨酸激酶，定位于 当细胞在底物上扩散时，导致局部粘连。Pp125(FAK)为 在许多增生性疾病中被许多不同的细胞外刺激激活 或致癌细胞，例如细胞外基质蛋白、生长因子、 神经肽和溶血磷脂酸(LPA)。除了这些之外， 细胞外刺激时，FAK与 Pp60(Src)在src转化的细胞中，FAK可能是底物之一。 V-src。Pp125(FAK)似乎在调节 由不同的相互作用引发的信令事件 细胞外刺激和膜-细胞骨架蛋白。此外， 此外，FAK在神经系统中的作用尚不清楚。这个 这项提案的具体目的是为了调查 利用生化、分子和生物化学相结合的方法在大鼠脑内检测pp125(FAK)。 和免疫学技术。研究FAK在细胞周期调控中的作用 大脑，我计划：1)确定FAK的表达模式及其亚细胞 发育不同阶段大鼠脑的分布；2) 鉴定与大鼠FAK相互作用的蛋白质 3)研究FAK酪氨酸活化的机制 大鼠大脑中的激酶活性。

The objective of the proposed research is to characterize the roles of the Focal Adhesion Kinase (FAK) in rat central nervous system. Focal adhesion kinase, a 125-kDa cytoplasmic protein tyrosine kinase, localizes to focal adhesions when cells spread on a substratum. pp125(FAK) is activated by many different extracellular stimuli in many proliferative or oncogenic cells, e.g., extracellular matrix proteins, growth factors, neuropeptides, and lysophosphatidic acid (LPA). In addition to these extracellular stimuli, there is a stable association of FAK with pp60(src) in src transformed cells, and FAK may be one of the substrates of v-src. pp125(FAK) appears to play important roles in regulating signalling events initiated by the interactions of different extracellular stimuli and membrane-cytoskeleton proteins. Furthermore, in addition to functions of FAK in the nervous system is not clear. The specific aims of this proposal are designed to investigate the functions of pp125(FAK) in rat brain using a combination of biochemical, molecular, and immunological techniques. To study the functions of FAK in the brain, I plan to: 1)Determine FAK expression pattern and its subcellular distribution in rat brain at different stages during development; 2) Characterize and identify the proteins that interact with FAK in rat brain; 3) Investigate the mechanisms of the activation of FAK tyrosine kinase activity in the rat brain.