Transmembrane Signaling through Voltage-gated Ca Channel

通过电压门控 Ca 通道的跨膜信号传导

• 批准号: 7174363
• 负责人: Lutz Birnbaumer
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7174363
• 关键词: G protein; biological signal transduction; calcium channel; calcium channel blockers; dihydropyridines; electrophysiology; gene induction /repression; mass spectrometry; membrane activity; phosphorylation; protein kinase A; serine; voltage /patch clamp; voltage gated channel

The importance of a serine at the inner mouth of the channel (end of domain IV S6 segment) was studied. Its mutation to alanine abrogated the ability of the channel to enter into mode 2 gating upon stimulation by activation of PKA or addition of BAY-K8644. The serine (Ser 1517) may be a key regulatory site that determines, in coordination with the previously studied Ser 1142 in the selectivity filter, the responsivenes of the channel to phosphorylation and the dihydropyridine agonist. We are testing the hypothesis that loss of mode 2 gating is due to establshment of an ionic bridge between Ser 1517 and one of two nearby lysines from domain I, thus "freezing" the channel in mode 1 gating.

研究了通道内口（S6结构域末端）丝氨酸的重要性。它的丙氨酸突变取消了通道在激活PKA或添加BAY-K8644的刺激下进入模式2门控的能力。丝氨酸（Ser 1517）可能是一个关键的调控位点，它与先前研究的选择性过滤器中的Ser 1142协同决定通道对磷酸化和二氢吡啶激动剂的响应。我们正在测试一种假设，即模式2门控的损失是由于在Ser 1517和来自I域的两个附近赖氨酸中的一个之间建立了离子桥，从而将通道“冻结”在模式1门控中。