Cell Signaling

Tweaked Receptors

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Science  19 Aug 2011:
Vol. 333, Issue 6045, pp. 920
DOI: 10.1126/science.333.6045.920-c

β2-adrenergic receptors (β2ARs) are important drug targets in humans, mediating, for example, effects of drugs that help restore lung function in patients with asthma. There are common mutant forms of the β2AR gene in humans, though, and some of these can prevent such beneficial therapeutic actions. Using cultured human cells, Ahles et al. examined the signaling by common variants of β2AR, including one variant in which Arg16 is replaced by Gly. The response time of these receptors was similar to that of wild-type receptors after a single exposure to an agonist, but differed in response when exposed to repeated stimulation. The receptors with Gly16 were activated more rapidly after a second exposure to epinephrine, whereas the wild-type receptors responded more slowly to the second stimulus. The variant receptors with Gly16 also caused formation of greater amounts of the second messenger adenosine 3′-5′-monosphosphate, which would lead to enhanced downstream signaling. These results may explain why asthma patients who have the Gly variant respond better to β-agonist bronchodilator therapy.

Sci. Signal. 4, ra53 (2011).

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