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Differential capacities of the RGS1, RGS16 and RGS–GAIP regulators of G protein signaling to enhance α 2A ‐adrenoreceptor agonist‐stimulated GTPase activity of G o1 α
Author(s) -
Hoffmann Marcel,
Ward Richard J.,
Cavalli Antonella,
Carr I. Craig,
Milligan Graeme
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00479.x
Subject(s) - oxymetazoline , rgs2 , partial agonist , agonist , intrinsic activity , chemistry , g protein , receptor , microbiology and biotechnology , medicine , endocrinology , gtpase activating protein , biochemistry , biology
Recombinant RGS1, RGS16 and RGS–GAIP, but not RGS2, were able to substantially further stimulate the maximal GTPase activity of G o1 α promoted by agonists at the α 2A ‐adrenoreceptor in a concentration‐dependent manner. Kinetic analysis of the regulation of an α 2A ‐adrenoreceptor–G o1 α fusion protein by all three RGS proteins revealed that they had similar affinities for the receptor–G protein fusion. However, their maximal effects on GTP hydrolysis varied over threefold with RGS16 > RGS1 > RGS–GAIP. Both RGS1 and RGS16 reduced the potency of the α 2A ‐adrenoreceptor agonist adrenaline by some 10‐fold. A lower potency shift was observed for the partial agonist UK14304 and the effect was absent for the weak partial agonist oxymetazoline. Each of these RGS proteins altered the intrinsic activity of both UK14304 and oxymetazoline relative to adrenaline. Such results require the RGS interaction with G o1 α to alter the conformation of the α 2A ‐adrenoreceptor and are thus consistent with models invoking direct interactions between RGS proteins and receptors. These studies demonstrate that RGS1, RGS16 and RGS–GAIP show a high degree of selectivity to regulate α 2A ‐adrenoreceptor‐activated G o1 α rather than G i1 α, G i2 α or G i3 α and different capacities to inactivate this G protein.