cd15250

class F frizzled subfamily 8, member of 7-transmembrane G protein-coupled receptors

CDD entry
Member databaseCDD
CDD typedomain
Short name7tmF_FZD8
Set7tm_GPCRs

Description

This group includes subfamily 8 of the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate class of GPCRs, and its closely related proteins. This class F protein family consists of 10 isoforms (FZD1-10) in mammals. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The conserved cytoplasmic motif of FZD, Lys-Thr-X-X-X-Trp, is required for activation of the WNT/beta-catenin pathway, and for membrane localization and phosphorylation of Dsh (dishevelled) protein, a key component of the WNT pathway that relays the WNT signals from the activated receptor to downstream effector proteins. The WNT pathway plays a critical role in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.
[10, 8, 15, 5, 22, 14, 12, 7, 13, 4, 9, 3, 2, 21, 19, 1, 6, 20, 18, 11, 16, 17]

References

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4.G proteins in signal transduction. Birnbaumer L. Annu. Rev. Pharmacol. Toxicol. 30, 675-705, (1990). View articlePMID: 2111655

5.The Frizzled family: receptors for multiple signal transduction pathways. Huang HC, Klein PS. Genome Biol. 5, 234, (2004). View articlePMID: 15239825

6.The GPCR Network: a large-scale collaboration to determine human GPCR structure and function. Stevens RC, Cherezov V, Katritch V, Abagyan R, Kuhn P, Rosen H, Wuthrich K. Nat Rev Drug Discov 12, 25-34, (2013). View articlePMID: 23237917

7.Learning from the past: evolution of GPCR functions. Schoneberg T, Hofreiter M, Schulz A, Rompler H. Trends Pharmacol. Sci. 28, 117-21, (2007). View articlePMID: 17280721

8.In vivo evidence that Patched and Smoothened constitute distinct binding and transducing components of a Hedgehog receptor complex. Chen Y, Struhl G. Development 125, 4943-8, (1998). View articlePMID: 9811578

9.G protein-coupled receptor deorphanizations. Civelli O, Reinscheid RK, Zhang Y, Wang Z, Fredriksson R, Schioth HB. Annu. Rev. Pharmacol. Toxicol. 53, 127-46, (2013). PMID: 23020293

10.A new member of the frizzled family from Drosophila functions as a Wingless receptor. Bhanot P, Brink M, Samos CH, Hsieh JC, Wang Y, Macke JP, Andrew D, Nathans J, Nusse R. Nature 382, 225-30, (1996). View articlePMID: 8717036

11.The origin of GPCRs: identification of mammalian like Rhodopsin, Adhesion, Glutamate and Frizzled GPCRs in fungi. Krishnan A, Almen MS, Fredriksson R, Schioth HB. PLoS ONE 7, e29817, (2012). View articlePMID: 22238661

12.Frizzleds: new members of the superfamily of G-protein-coupled receptors. Malbon CC. Front. Biosci. 9, 1048-58, (2004). View articlePMID: 14977528

13.Structure-function of the G protein-coupled receptor superfamily. Katritch V, Cherezov V, Stevens RC. Annu. Rev. Pharmacol. Toxicol. 53, 531-56, (2013). View articlePMID: 23140243

14.International Union of Basic and Clinical Pharmacology. LXXX. The class Frizzled receptors. Schulte G. Pharmacol Rev 62, 632-67, (2010). PMID: 21079039

15.The frizzled motif: in how many different protein families does it occur? Rehn M, Pihlajaniemi T, Hofmann K, Bucher P. Trends Biochem. Sci. 23, 415-7, (1998). View articlePMID: 9852758

16.Evolution of GPCR: change and continuity. Strotmann R, Schrock K, Boselt I, Staubert C, Russ A, Schoneberg T. Mol Cell Endocrinol 331, 170-8, (2011). PMID: 20708652

17.[Structure of the Smoothened receptor]. Ruat M, Hoch L, Faure H, Rognan D. Med Sci (Paris) 29, 855-60, (2013). View articlePMID: 24148123

18.Comparative sequence and structural analyses of G-protein-coupled receptor crystal structures and implications for molecular models. Worth CL, Kleinau G, Krause G. PLoS ONE 4, e7011, (2009). View articlePMID: 19756152

19.G protein-coupled receptors--recent advances. Latek D, Modzelewska A, Trzaskowski B, Palczewski K, Filipek S. Acta Biochim. Pol. 59, 515-29, (2012). PMID: 23251911

20.G-protein-coupled receptor structure, ligand binding and activation as studied by solid-state NMR spectroscopy. Ding X, Zhao X, Watts A. Biochem J 450, 443-57, (2013). PMID: 23445222

21.Molecular signatures of G-protein-coupled receptors. Venkatakrishnan AJ, Deupi X, Lebon G, Tate CG, Schertler GF, Babu MM. Nature 494, 185-94, (2013). View articlePMID: 23407534

22.The Wnt/Frizzled GPCR signaling pathway. Katanaev VL. Biochemistry Mosc. 75, 1428-34, (2010). View articlePMID: 21314612

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