Phosphorylation Provides a Negative Mode of Regulation for the Yeast Rab GTPase Sec4p

The Rab family of Ras-related GTPases are part of a complex signaling circuitry in eukaryotic cells, yet we understand little about the mechanisms that underlie Rab protein participation in such signal transduction networks, or how these networks are integrated at the physiological level. Reversible protein phosphorylation is widely used by cells as a signaling mechanism. Several phospho-Rabs have been identified, however the functional consequences of the modification appear to be diverse and need to be evaluated on an individual basis. In this study we demonstrate a role for phosphorylation as a negative regulatory event for the action of the yeast Rab GTPase Sec4p in regulating polarized growth. Our data suggest that the phosphorylation of the Rab Sec4p prevents interactions with its effector, the exocyst component Sec15p, and that the inhibition may be relieved by a PP2A phosphatase complex containing the regulatory subunit Cdc55p.

Ras相关GTP酶（Ras-related GTPases）的Rab家族是真核细胞复杂信号传导回路的组成部分，然而目前我们对Rab蛋白参与此类信号转导网络的分子机制，以及这些网络在生理层面的整合方式仍所知有限。可逆蛋白质磷酸化是细胞广泛采用的信号传导机制。目前已鉴定出多种磷酸化Rab蛋白，但该修饰的功能效应呈现多样性，需针对单个Rab蛋白逐一评估。本研究证实，磷酸化可作为负调控事件，参与酵母Rab GTP酶Sec4p调控极性生长的过程。我们的数据表明，Rab蛋白Sec4p的磷酸化会阻碍其与效应蛋白——胞泌复合体（exocyst）组分Sec15p的相互作用，而这种抑制作用可被含有调节亚基Cdc55p的PP2A磷酸酶复合物所解除。