RGULATION OF CYCLIC GMP PHOSPHODIESTERASE BY GZ

我们对细胞如何传递信息的理解已经取得了很大进展 外部信号通过特定的细胞表面受体传递到内部 目标的 受体结合启动细胞内信号传导途径， 通常通过激活异源三聚体G蛋白， 导致特定的细胞反应。 GZ是一种这样的异源三聚体 具有独特生化特征和有限组织的G蛋白 分布 虽然Gz的初步特征已经提供了 深入了解蛋白质的生化特性， Gz的下游靶点仍不确定。初步研究 利用酵母双杂交系统表明，Gzalpha可能 与环GMP磷酸二酯酶的γ亚基相互作用。 G-的 磷酸二酯酶的蛋白质调节在外界还没有被描述 感觉组织，但最近的鉴定Gz和 大脑不同区域的磷酸二酯酶γ支持 认为这可能发生。 我们假设磷酸二酯酶γ Gz的天然效应子。 体外研究和完整的 将进行细胞以确定磷酸二酯酶γ和 Gzalpha相关以及这种相互作用是否可以调节循环 通过激活磷酸二酯酶复合物来提高核苷酸水平。 的 拟议中的研究很可能会导致第一次 表征Gzalpha与特定效应物的相互作用 分子，即磷酸二酯酶γ。

Much progress has been made in our understanding of how cells transmit external signals via specific cell surface receptors to internal targets. Receptor binding initiates intracellular signaling pathways, often through the activation of heterotrimeric G-proteins, eventually leading to a specific cellular response. Gz is one such heterotrimeric G-protein that exhibits unique biochemical features and limited tissue distribution. Although initial characterization of Gz has provided insight into the biochemical characterization of the protein, the downstream target(s) of Gz remain undefined. Preliminary studies utilizing the yeast two-hybrid system suggest that Gzalpha may possibly interact with the gamma subunit of cyclic GMP phosphodiesterase. G- protein regulation of phosphodiesterases has not been described outside sensory tissues, but recent identification of both Gz and phosphodiesterase gamma in various regions of the brain supports the view that this may occur. We postulate that phosphodiesterase gamma is a natural effector for Gz. Both in vitro studies and studies in intact cells will be conducted to determine whether phosphodiesterase gamma and Gzalpha associate and whether this interaction can modulate cyclic nucleotide levels by activating the phosphodiesterase complex. The proposed studies will quite possibly result in the first characterization the interaction of Gzalpha with a specific effector molecule, namely phosphodiesterase gamma.