13. Liu Z, Habener JF (2008) Glucagon-like peptide-1 activation of TCF7L2- dependent Wnt signaling enhances pancreatic beta cell proliferation. J Biol Chem 283: 8723–8735. 14. Wan M, Yang C, Li J, Wu X, Yuan H, et al. (2008) Parathyroid hormone signaling through low-density lipoprotein-related protein 6. Genes Dev 22: 2968–2979. 15. Romero G, Sneddon WB, Yang Y, Wheeler D, Blair HC, et al. (2010) Parathyroid hormone receptor directly interacts with dishevelled to regulate beta-Catenin signaling and osteoclastogenesis. J Biol Chem 285: 14756–14763. 16. Fujino T, Asaba H, Kang MJ, Ikeda Y, Sone H, et al. (2003) Low-density lipoprotein receptor-related protein 5 (LRP5) is essential for normal cholesterol metabolism and glucose-induced insulin secretion. Proc Natl Acad Sci U S A 100: 229–234. 17. Mani A, Radhakrishnan J, Wang H, Mani A, Mani MA, et al. (2007) LRP6 mutation in a family with early coronary disease and metabolic risk factors. Science 315: 1278–1282. 18. Xu Q, Wang Y, Dabdoub A, Smallwood PM, Williams J, et al. (2004) Vascular development in the retina and inner ear: control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair. Cell 116: 883–895. 19. Wan M, Li J, Herbst K, Zhang J, Yu B, et al. (2011) LRP6 mediates cAMP generation by G protein-coupled receptors through regulating the membrane targeting of Galpha(s). Sci Signal 4: ra15. 20. Burcelin R, Mrejen C, Decaux JF, De Mouzon SH, Girard J, et al. (1998) In vivo and in vitro regulation of hepatic glucagon receptor mRNA concentration by glucose metabolism. J Biol Chem 273: 8088–8093. 21. Gong Y, Slee RB, Fukai N, Rawadi G, Roman-Roman S, et al. (2001) LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell 107: 513–523. 22. Mao J, Wang J, Liu B, Pan W, Farr GH, 3rd, et al. (2001) Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway. Mol Cell 7: 801–809. 23. Shevtsov SP, Haq S, Force T (2006) Activation of beta-catenin signaling pathways by classical G-protein-coupled receptors: mechanisms and conse- quences in cycling and non-cycling cells. Cell Cycle 5: 2295–2300. 24. Barnes MR, Duckworth DM, Beeley LJ (1998) Frizzled proteins constitute a novel family of G protein-coupled receptors, most closely related to the secretin family. Trends Pharmacol Sci 19: 399–400. Glucagon Induced b-Catenin Signaling Pathway 25. Cong F, Schweizer L, Varmus H (2004) Wnt signals across the plasma membrane to activate the beta-catenin pathway by forming oligomers containing its receptors, Frizzled and LRP. Development 131: 5103–5115. 26. Umbhauer M, Djiane A, Goisset C, Penzo-Mendez A, Riou JF, et al. (2000) The C-terminal cytoplasmic Lys-thr-X-X-X-Trp motif in frizzled receptors mediates Wnt/beta-catenin signalling. Embo J 19: 4944–4954. 27. Welters HJ, Kulkarni RN (2008) Wnt signaling: relevance to beta-cell biology and diabetes. Trends Endocrinol Metab 19: 349–355. 28. Grant SF, Thorleifsson G, Reynisdottir I, Benediktsson R, Manolescu A, et al. (2006) Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat Genet 38: 320–323. 29. Holmen SL, Robertson SA, Zylstra CR, Williams BO (2005) Wnt-independent activation of beta-catenin mediated by a Dkk1-Fz5 fusion protein. Biochem Biophys Res Commun 328: 533–539. 30. Holmen SL, Salic A, Zylstra CR, Kirschner MW, Williams BO (2002) A novel set of Wnt-Frizzled fusion proteins identifies receptor components that activate beta -catenin-dependent signaling. J Biol Chem 277: 34727–34735. 31. Lin J, Wu PH, Tarr PT, Lindenberg KS, St-Pierre J, et al. (2004) Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha mice. Cell 119: 121–135. 32. Ke J, Chelvarajan RL, Sindhava V, Robertson DA, Lekakis L, et al. (2009) Anomalous constitutive Src kinase activity promotes B lymphoma survival and growth. Mol Cancer 8: 132. 33. Harikumar KG, Pinon DI, Miller LJ (2007) Transmembrane segment IV contributes a functionally important interface for oligomerization of the Class II G protein-coupled secretin receptor. J Biol Chem 282: 30363–30372. 34. Cheng ZJ, Miller LJ (2001) Agonist-dependent dissociation of oligomeric complexes of G protein-coupled cholecystokinin receptors demonstrated in living cells using bioluminescence resonance energy transfer. J Biol Chem 276: 48040–48047. 35. Tusnady GE, Simon I (2001) The HMMTOP transmembrane topology prediction server. Bioinformatics 17: 849–850. 36. Thompson JD, Higgins DG, Gibson TJ (1994) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22: 4673–4680. PLoS ONE | www.plosone.org 11 March 2012 | Volume 7 | Issue 3 | e33676