Rap1/Krev1 is a member of the ras family of
low molecular weight GTP-binding proteins. Ras-like GTPases are
ubiquitously
expressed, evolutionarily conserved molecular switches that couple
extracellular signals to various cellular responses. Rap1 is
primarily found at the cytosolic side of intracellular membranes
and has two isoforms: Rap1a and 1b. Both isoforms have a molecular
mass of 21 kDa and are isoprenylated at the carboxyl-terminal and
phosphorylated by the cAMP-dependent protein kinase A (PKA).
Rap1 cycles between a GTP-bound active form and a GDP-bound inactive
form that is mediated by GTPase activating protein (GAP)
and GDP dissociation stimulator (GDS). Activation occurs by a variety
of extracellular stimuli through several conserved guanine
nucleotide exchange factors (GEFs) and GTPase activating proteins
(GAPs). Rap1 is proposed to regulate Ras-mediated signalling and
may also be involved in the regulation of integrin-mediated cell
adhesion although the mechanism of regulation is not known.
Overexpression of Rap reverses the transformed phenotype induced
by ras, possibly by competing with ras for interaction with ras-GAP.
Rap has been shown to participate in MAP kinase cascade activated
by growth factor and maintaining human T cell anergic state by
blocking IL-2 expression.
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