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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