ADVERTISEMENT
ADVERTISEMENT

Bifunctional signaling proteins

Credit: Kenneth Eward / Photo Researchers, Inc" /> Credit: Kenneth Eward / Photo Researchers, Inc The paper: S. Shenoy et al., "β-Arrestin-dependent, G protein-independent ERK1/2 activation by the β2 adrenergic receptor," J Biol Chem, 281:1261-73, 2006. (Cited in 50 papers) The finding: In 2005, while screening for G protein-independent arrestin signaling on the widely studied ERK pathway, Robert Lefkowitz's group at Duke University

Andrea Gawrylewski
<figcaption> Credit: Kenneth Eward / Photo Researchers, Inc</figcaption>
Credit: Kenneth Eward / Photo Researchers, Inc

The paper:
S. Shenoy et al., "β-Arrestin-dependent, G protein-independent ERK1/2 activation by the β2 adrenergic receptor," J Biol Chem, 281:1261-73, 2006. (Cited in 50 papers)

The finding:
In 2005, while screening for G protein-independent arrestin signaling on the widely studied ERK pathway, Robert Lefkowitz's group at Duke University showed that β-arrestin can activate the β2-adrenergic receptor (β2AR), a receptor previously found only to be suppressed by arrestin.

The strategy:
The team blocked the G protein-dependent portion of the signaling pathway by using three separate inhibitors, in addition to knocking out G protein coupling. This paper exhaustively demonstrated that "arrestin clearly is capable of activating ERK" by signaling the β2AR pathway, says Jeffrey Benovic at Thomas Jefferson University in Philadelphia, and former protégé of Lefkowitz.

The follow up:
Lefkowitz and others are now looking at the physiologic differences that result from the separate...

Other G protein-dependent pathways activated by β-arrestin:
Chemotaxis: Mol Pharm, 67:1229-36, 2005
β1AR (via ERK MAPK signaling): J Clin Invest, 117:2445-58, 2007
Actin cytoskeletal assembly: J Biol Chem, 282:20634-46, 2007

Interested in reading more?

Magaizne Cover

Become a Member of

Receive full access to digital editions of The Scientist, as well as TS Digest, feature stories, more than 35 years of archives, and much more!
Already a member?
ADVERTISEMENT