Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Sci. Signal., 15 March 2011
Vol. 4, Issue 164, p. ra15
[DOI: 10.1126/scisignal.2001464]

RESEARCH ARTICLES

Editor's Summary

Unexpected Partner
Signaling by heterotrimeric guanine nucleotide–binding protein (G protein)–coupled receptors (GPCRs) that respond to hormones, such as parathyroid hormone receptor 1 (PTH1R), has been extensively characterized. Ligand binding to the certain classes of GPCRs results in the activation of G proteins that contain the Gαs subunit, which stimulates the effector adenylyl cyclase (AC) to generate the second messenger (cAMP). Wan et al. have shown that low-density lipoprotein receptor–related protein 6 (LRP6), a transmembrane co-receptor for Wnt proteins, was required for efficient activation of Gαs-mediated cAMP signaling by various GPCRs, including PTH1R, through a mechanism that involved LRP6-mediated recruitment of Gαs-containing G proteins to receptors at the plasma membrane. PKA, a kinase activated by cAMP, phosphorylated LRP6, which enhanced its binding to Gαs. AC is the therapeutic target in the treatment of various hormonal disorders; the data of Wan et al. suggest that modulation of LRP6 activity may provide an additional strategy.

Citation: M. Wan, J. Li, K. Herbst, J. Zhang, B. Yu, X. Wu, T. Qiu, W. Lei, C. Lindvall, B. O. Williams, H. Ma, F. Zhang, X. Cao, LRP6 Mediates cAMP Generation by G Protein–Coupled Receptors Through Regulating the Membrane Targeting of Gαs. Sci. Signal. 4, ra15 (2011).

Read the Full Text

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Inhibitory Mechanism of an Allosteric Antibody Targeting the Glucagon Receptor.
S. Mukund, Y. Shang, H. J. Clarke, A. Madjidi, J. E. Corn, L. Kates, G. Kolumam, V. Chiang, E. Luis, J. Murray, et al. (2013)
J. Biol. Chem. 288, 36168-36178
   Abstract »    Full Text »    PDF »
Nuclear Receptors in Bone Physiology and Diseases.
Y. Imai, M.-Y. Youn, K. Inoue, I. Takada, A. Kouzmenko, and S. Kato (2013)
Physiol Rev 93, 481-523
   Abstract »    Full Text »    PDF »
Frizzled and LRP5/6 Receptors for Wnt/{beta}-Catenin Signaling.
B. T. MacDonald and X. He (2012)
Cold Spring Harb Perspect Biol 4, a007880
   Abstract »    Full Text »    PDF »
Parathyroid hormone-related protein activates Wnt signaling to specify the embryonic mammary mesenchyme.
M. Hiremath, P. Dann, J. Fischer, D. Butterworth, K. Boras-Granic, J. Hens, J. Van Houten, W. Shi, and J. Wysolmerski (2012)
Development 139, 4239-4249
   Abstract »    Full Text »    PDF »
Fluorescence/Bioluminescence Resonance Energy Transfer Techniques to Study G-Protein-Coupled Receptor Activation and Signaling.
M. J. Lohse, S. Nuber, and C. Hoffmann (2012)
Pharmacol. Rev. 64, 299-336
   Abstract »    Full Text »    PDF »
p53 and MicroRNA-34 Are Suppressors of Canonical Wnt Signaling.
N. H. Kim, H. S. Kim, N.-G. Kim, I. Lee, H.-S. Choi, X.-Y. Li, S. E. Kang, S. Y. Cha, J. K. Ryu, J. M. Na, et al. (2011)
Science Signaling 4, ra71
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882