MODULATION OF VOLTAGE DEPENDENT POTASSIUM CHANNELS

描述（改编自研究者的应用程序）：离子通道 破坏了一类特殊的膜蛋白， 在神经、肌肉和其他细胞中发出信号。 离子通道的调节 性质，特别是蛋白质磷酸化，是基本的 对许多细胞类型的功能至关重要。 虽然 已经研究了离子通道的丝氨酸/苏氨酸磷酸化 彻底地，通过酪氨酸磷酸化调节离子通道， 大部分未开发。 研究人员建议检查调节性 蛋白酪氨酸激酶与电压门控钾离子相互作用 (Kv)渠道 调查人员将重点调查两名代表成员 Kv通道家族：Dv1.3，在T淋巴细胞中突出， 一些脑神经元和Kv1.5，其在心脏和脑中高度表达。 该提案将测试两个假设，每个假设都基于广泛的 初步数据。 第一个是一些Kv通道可以紧密结合 与酪氨酸激酶在一个调节复合物，第二个是， 是Kv通道和酪氨酸激酶的相互调节-也就是说， 通道和激酶可以相互调节彼此的活动。 的 研究者的具体目标是：1）研究分子 Kv通道直接结合的机制和功能后果 和酪氨酸激酶; 2）研究分子机制， 酪氨酸磷酸化调节Kv通道电流;和3） 研究Kv通道和酪氨酸激酶的相互调节。 克隆的Kv1.3和Kv1.5的性质将在其 在人胚肾（HEK 293细胞系，和 在培养的嗅球中研究天然Kv通道电流 神经元 对于这些具体目标中的每一个，研究人员将使用 生物化学、生理学和分子方法的组合， 剖析调节的分子细节和功能后果， Kv通道和酪氨酸激酶之间的相互作用。

DESCRIPTION (Adapted from the investigator's application): Ion channels compromise a specialized class of membrane proteins that underlie electrical signalling in nerve, muscle and other cells. Modulation of ion channels properties, particularly by protein phosphorylation, is of fundamental importance for the functioning of many cell types. Although serine/threonine phosphorylation of ion channels has been studied thoroughly, modulation of ion channels by tyrosine phosphorylation is largely unexplored. The investigator proposes to examine modulatory interactions between protein tyrosine kinases and voltage-gated potassium (Kv) channels. The investigators will focus on two representative members of the Kv channel family: Dv1.3, which is prominent in T lymphocytes and some brain neurons, and Kv1.5, which is expressed highly in heart and brain. This proposal will test two hypotheses, each of which is based on extensive preliminary data. The first is that some Kv channels can associate tightly with tyrosine kinases in a regulatory complex, and the second is that there is reciprocal regulation of Kv channels and tyrosine kinases - that is, channels and kinases can regulate each other's activities. The investigator's specific aims are: 1) To investigate the molecular mechanisms and functional consequences of direct association of Kv channels and tyrosine kinases; 2) to investigate the molecular mechanisms by which tyrosine phosphorylation modulates Kv channels current; and 3) to investigate the reciprocal regulation of Kv channels and tyrosine kinsases. The properties of cloned Kv1.3 and Kv1.5 will be examined following their heterologous expression in a human embryonic kidney (HEK 293 cell line, and native Kv channel current will be investigated in cultured olfactory bulb neurons. For each of these specific aims, the investigators will use a combination of biochemical, physiological and molecular approaches to dissect the molecular details and functional consequences of modulatory interactions between Kv channels and tyrosine kinases.