<p> Small GTPases of the Ras family alternate between 2 conformations induced by the binding of either GTP or GDP. Guanine nucleotide exchange factors (GEFs) induce the dissociation of GDP to allow association of the more abundant GTP. The Ras-like family of small GTPases includes, among others, Ras, Rap1, R-ras, and Ral. The family is characterised by similarities in the effector domain. The Ras GTPase 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. GEFs have been identified that mediate these effects. One such GEF is Epac, an exchange protein directly activated by cAMP, which represents a novel cAMP-induced, protein kinase A-independent pathway [<cite idref="PUB00010624"/>].</p>