SIGNAL TRANSDUCTION BY PROTEIN PHOSPHORYLATION

我们建议继续研究细胞过程的调节 通过蛋白质磷酸化，特别是对结构、功能和 蛋白酪氨酸磷酸酶（PTPs）的调节。 PTPs现在 已知其代表了细胞内和细胞外的一个大而多样的家族， 受体连接酶 可以假设它们在 调节这些激素引发的多种事件， 具有内在蛋白酪氨酸激酶的生长因子受体 活动和微调的高度集成电路，调节 真核细胞 我们的主要目标是研究：a）结构，性质 和调节细胞内和受体连接的酶; B） 酪氨酸、丝氨酸和苏氨酸之间必然存在相互作用 c）PTP的亚细胞定位和它们的磷酸化作用; 参与细胞周期和细胞骨架重组;和d） 它们在阻断或逆转细胞转化中的可能功能。 一个试图解释磷酸酶如何起作用的假说 与激酶协同作用以引发完整的生理反应， 无论靶蛋白的磷酸化状态如何， 得到考验

We propose to continue our studies o the regulation of cellular processes by protein phosphorylation, particularly on the structure, function and regulation of protein tyrosine phosphatase (PTPs). The PTPs are now known to represent a large and diverse family of intracellular and receptor-linked enzymes. It can be assumed they play an essential role in regulating the multiplicity of events initiated by those hormone and growth factor receptors possessing intrinsic protein tyrosine kinase activity and in fine-tuning the highly integrated circuits that regulate eukaryotic cells. Our main goal is to study: a) structure, properties and regulation of the intracellular and receptor-linked enzymes; b) interplay that must exist between tyrosine and serine and threonine phosphorylation; c) subcellular localization of the PTPs and their involvement in the cell cycle and cytoskeleton reorganization; and d) their possible function in blocking or reversing cell transformation. A hypothesis attempting to explain how phosphatases might act synergistically with the kinases to elicit a full physiological response, irrespective of the state of phosphorylation of the target protein, will be tested.