IDENTIFICATION OF MAMMALIAN HISTIDINE KINASES

了解细胞从细胞中传递信号的机制， 细胞外环境是至关重要的理解正常以及 异常的细胞生长蛋白质磷酸化与 在传递由许多不同类型的细胞外 刺激。真核生物信号通路的研究主要集中在 丝氨酸，苏氨酸和酪氨酸磷酸化的贡献 proteins. 从许多实验室收集的数据表明， 磷酸组氨酸是哺乳动物细胞蛋白质的重要组分。 组氨酸激酶和磷酸酶已经涉及哺乳动物中的 在几个体外研究中的信号通路。最近，瞬时蛋白 组氨酸磷酸化已在体内被证实， 由凝血酶或胶原刺激引发的信号传导途径 血小板组氨酸的分子效应的评价 哺乳动物信号的磷酸化需要鉴定 组氨酸激酶。这个项目的重点是生物化学 哺乳动物组氨酸激酶的纯化及其分子克隆 内切酶这些研究有可能为以下领域提供新的线索： 真核细胞信号转导

Knowledge of the mechanisms cells use to transmit signals from the extracellular environment is crucial in understanding normal as well as aberrant cellular growth. Protein phosphorylation is intricately involved in transmitting signals initiated by many different types of extracellular stimuli. Studies of eukaryotic signaling pathways have focused on the contributions of serine, threonine and tyrosine phosphorylation of proteins. Data gathered from many laboratories indicate that phosphohistidine is a significant component of mammalian cellular protein. Histidine kinases and phosphatases have been implicated in mammalian signaling pathways in several in vitro studies. Recently, transient protein histidine phosphorylation has been demonstrated in vivo, in response to signaling pathways initiated by thrombin or collagen stimulation of human platelets. Appreciation of the molecular consequences of histidine phosphorylation for mammalian signaling requires identification of histidine kinases. The focus of this project is the biochemical purification of mammalian histidine kinases and molecular cloning of these enzymes. These studies have the potential to shed new light on the field of eukaryotic signal transduction.