Activation of Rap1 by membrane-associated GEFs

Signals from agonist receptors (such as GPVI) trigger the production of PIP3, DAG, cAMP and elevated Ca++ levels. This leads to the activation and translocation of active Rap1-GTP to the plasma membrane. Rap-GEFs stimulate the replacement of GDP for GTP, activating Rap1. Several Rap1 GEFs have been identified enabling Rap1 to respond to diverse stimuli. CalDAG-GEFs activate Rap1 in response to calcium and DAG, downstream of Phospholipase C. EPAC (exchange proteins directly activated by cAMP) GEFs are activated by binding cAMP.

激动剂受体（如GPVI）所发出的信号触发了PIP3、DAG、cAMP的产生及Ca++水平的升高。此过程导致活性Rap1-GTP在质膜上的激活与转移。Rap-GEFs（Rap1 GEFs）通过将GDP替换为GTP，激活Rap1。已鉴定出多种Rap1 GEFs，使Rap1能够对多种刺激作出响应。CalDAG-GEFs在磷脂酶C下游，对钙和DAG的反应中激活Rap1。EPAC（由cAMP直接激活的交换蛋白）GEFs通过结合cAMP而被激活。