Ras and Rap1: two highly related small GTPases with distinct function.
The Ras-like family of small GTPases includes, among others, Ras, Rap1, R-ras, and Ral. The family is characterized by similarities in the effector domain. While the function of Ras is, at least in part, elucidated, little is known about other members of the family. Currently, much attention is focused on the small GTPase Rap1. Initially, this member was identified as a transformation suppressor protein able to revert the morphological phenotype of Ras-transformed fibroblasts. This has led to the hypothesis that Rap1 antagonizes Ras by interfering in Ras effector function. Recent analysis revealed that Rap1 is activated rapidly in response to activation of a variety of receptors. Rap1 activation is mediated by several second messengers, including calcium, diacylglycerol, and cAMP. Guanine nucleotide exchange factors (GEFs) have been identified that mediate these effects. The most interesting GEF is Epac, an exchange protein directly activated by cAMP, thus representing a novel cAMP-induced, protein kinase A-independent pathway. Furthermore, Rap1 is inactivated by specific GTPase-activating proteins (GAPs), one of which is regulated through an interaction with Galphai. While Ras and Rap1 may share some effector pathways, evidence is accumulating that Ras and Rap1 each regulate unique cellular processes in response to various extracellular ligands. For Rap1 these functions may include the control of cell morphology.
Zwartkruis
F J
FJ
Laboratory for Physiological Chemistry, Center for Biomedical Genetics, Utrecht University, Universiteitsweg 100, Utrecht, 3584 CG, The Netherlands.
Bos
J L
JL
D000595:Amino Acid Sequence; D002448:Cell Adhesion; D002451:Cell Compartmentation; D048429:Cell Size; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism*; D018631:ras Proteins / Q000378:metabolism*
D020558:GTP Phosphohydrolases; D020827:rap1 GTP-Binding Proteins; D018631:ras Proteins