Role of G(alpha)Z in pancreatic islet beta-cell biology

描述（由申请人提供）：异源三聚体G蛋白Gz控制神经内分泌细胞中一种不寻常的MAP激酶信号级联反应，该信号级联反应由Ras家族成员Rap 1激活触发。有趣的是，Gz在神经系统外表达的少数地方之一是胰腺中的胰岛细胞。此外，我们最近发现Gz信号的关键调节因子Rap 1GAP也在胰岛细胞中表达。鉴于G蛋白偶联受体在调节胰岛细胞生物学多个方面的重要性的证据，该数据暗示了Gz在胰腺的生理学和可能的病理生理学中的潜在非常重要的作用。本提案中描述的实验旨在开发用于解剖Gz在胰岛细胞中的生物学的分子工具，包括鉴定直接抑制Gz与我们已经鉴定的Rap 1调节因子Rap 1GAP之间相互作用的试剂，然后利用这些试剂和其他实验策略来定义Gz/Rap 1GAP相互作用在胰岛细胞生物学中重要的信号事件中的重要性。

DESCRIPTION (provided by applicant): The heterotrimeric G protein, Gz, controls an unusual MAP kinase signaling cascade in neuroendocrine cells that it triggered by activation of the Ras family member, Rap1. Interestingly, one of the few places that Gz is expressed outside of the nervous system is in islet cells in the pancreas. In addition, we have recently found that a key regulator of Gz signaling, Rap1GAP, is also expressed in islet cells. Given the evidence for the importance of G protein-coupled receptors in regulation of multiple aspects of islet cell biology, this data hints at potentially very important roles for Gz in the physiology, and possible pathophysiology, of the pancreas. The experiments described in this proposal aim to develop molecular tools for dissecting the biology of Gz in the pancreatic islet cells, including the identification of reagents that directly inhibit the interaction between Gz and the Rap1 regulator Rap1GAP that we have identified, and then utilize these reagents and other experimental strategies to define the importance of the Gz/Rap1GAP interaction in signaling events important in islet cell biology.