G protein signaling from activated rat frizzled-1 to the beta-catenin-Lef-Tcf pathway.
The frizzled receptors, which mediate development and display seven hydrophobic, membrane-spanning segments, are cell membrane-localized. We constructed a chimeric receptor with the ligand-binding and transmembrane segments from the beta2-adrenergic receptor (beta2AR) and the cytoplasmic domains from rat Frizzled-1 (Rfz1). Stimulation of mouse F9 clones expressing the chimera (beta2AR-Rfz1) with the beta-adrenergic agonist isoproterenol stimulated stabilization of beta-catenin, activation of a beta-catenin-sensitive promoter, and formation of primitive endoderm. The response was blocked by inactivation of pertussis toxin-sensitive, heterotrimeric guanine nucleotide-binding proteins (G proteins) and by depletion of Galphaq and Galphao. Thus, G proteins are elements of Wnt/Frizzled-1 signaling to the beta-catenin-lymphoid-enhancer factor (LEF)-T cell factor (Tcf) pathway.
Liu
T
T
Department of Molecular Pharmacology, Diabetes and Metabolic Diseases Research Center, University Medical Center, State University of New York at Stony Brook, Stony Brook, NY 11794-8651, USA.
DeCostanzo
A J
AJ
Liu
X
X
Wang Hy
Hallagan
S
S
Moon
R T
RT
Malbon
C C
CC
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D004707:Endoderm / Q000502:physiology; D051157:Frizzled Receptors; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D006160:Guanosine Triphosphate / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D007545:Isoproterenol / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D037342:Pertussis Toxin; D011433:Propranolol / Q000378:metabolism / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D017981:Receptors, Neurotransmitter / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D051153:Wnt Proteins; D014981:Xenopus; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
C495266:CTNNB1 protein, Xenopus; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; C489741:FZD1 protein, Xenopus; D051157:Frizzled Receptors; C489739:Fzd1 protein, mouse; D011518:Proto-Oncogene Proteins; D018343:Receptors, Adrenergic, beta-2; D043562:Receptors, G-Protein-Coupled; D017981:Receptors, Neurotransmitter; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D010566:Virulence Factors, Bordetella; D051153:Wnt Proteins; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; D006160:Guanosine Triphosphate; D011433:Propranolol; D037342:Pertussis Toxin; D020962:Heterotrimeric GTP-Binding Proteins; D007545:Isoproterenol