Rap1 GTPase: functions, regulation, and malignancy.

Rap1 is a member of the Ras family of small GTPases that is activated by diverse extracellular stimuli in many cell types. It is activated by distinct types of Rap1 guanine nucleotide exchange factors coupled with various receptors or second messengers, while activated Rap1 is down-regulated by Rap1 GTPase-activating proteins, through which Rap1 activation is controlled spatio-temporally. Functionally, Rap1 either interferes with Ras-mediated ERK activation or activates ERK independently of Ras in a cell-context dependent manner. Accumulating evidence also indicates that Rap1 is a major activator of integrins, playing important roles in the regulation of a variety of integrin-dependent cellular functions. Most recently, significant evidence has emerged that dysregulation of Rap1 activation is responsible for the development of malignancy. Recent extensive research has begun to unveil the roles of this controversial small G protein in physiology and diseases.