PMID- 10588714
OWN - NLM
STAT- MEDLINE
DCOM- 20000105
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 25
DP  - 1999 Dec 7
TI  - Activation of a frizzled-2/beta-adrenergic receptor chimera promotes Wnt
      signaling and differentiation of mouse F9 teratocarcinoma cells via Galphao and
      Galphat.
PG  - 14383-8
AB  - The frizzled gene family of putative Wnt receptors encodes proteins that have a
      seven-transmembrane-spanning motif characteristic of G protein-linked receptors, 
      though no loss-of-function studies have demonstrated a requirement for G proteins
      for Frizzled signaling. We engineered a Frizzled-2 chimera responsive to
      beta-adrenergic agonist by using the ligand-binding domains of the
      beta(2)-adrenergic receptor. The expectation was that the chimera would be
      sensitive both to drug-mediated activation and blockade, thereby circumventing
      the problem of purifying soluble and active Wnt ligand to activate Frizzled.
      Expression of the chimera in zebrafish embryos demonstrated isoproterenol
      (ISO)-stimulated, propranolol-sensitive calcium transients, thereby confirming
      the beta-adrenergic nature of Wnt signaling by the chimeric receptor. Because F9 
      embryonic teratocarcinoma cells form primitive endoderm after stable transfection
      of Frizzled-2 chimera and stimulation with ISO, they were subject to depletion of
      G protein subunits. ISO stimulation of endoderm formation of F9 stem cells
      expressing the chimeric receptor was blocked by pertussis toxin and by
      oligodeoxynucleotide antisense to Galphao, Galphat2, and Gbeta2. Our results
      demonstrate the requirement of two pertussis toxin-sensitive G proteins, Galphao 
      and Galphat, for signaling by the Frizzled-2 receptor.
FAU - Liu, X
AU  - Liu X
AD  - Department of Pharmacology, State University of New York, Stony Brook, NY
      11794-8651, USA.
FAU - Liu, T
AU  - Liu T
FAU - Slusarski, D C
AU  - Slusarski DC
FAU - Yang-Snyder, J
AU  - Yang-Snyder J
FAU - Malbon, C C
AU  - Malbon CC
FAU - Moon, R T
AU  - Moon RT
FAU - Wang, H
AU  - Wang H
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Frizzled Receptors)
RN  - 0 (Fzd2 protein, mouse)
RN  - 0 (Oligonucleotides, Antisense)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, Adrenergic, beta)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (Receptors, Neurotransmitter)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Wnt Proteins)
RN  - 0 (Zebrafish Proteins)
RN  - 0 (wnt8b protein, zebrafish)
RN  - 149748-10-7 (Fzd2 protein, rat)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - L628TT009W (Isoproterenol)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - CHO Cells
MH  - Cell Differentiation
MH  - Cricetinae
MH  - Frizzled Receptors
MH  - GTP-Binding Proteins/*physiology
MH  - Isoproterenol/pharmacology
MH  - Mice
MH  - Molecular Sequence Data
MH  - Oligonucleotides, Antisense/pharmacology
MH  - Phosphatidylinositol 3-Kinases/physiology
MH  - Proto-Oncogene Proteins/*physiology
MH  - Rats
MH  - Receptors, Adrenergic, beta/*physiology
MH  - Receptors, G-Protein-Coupled
MH  - Receptors, Neurotransmitter/*physiology
MH  - Recombinant Fusion Proteins/*physiology
MH  - Teratocarcinoma/*pathology
MH  - Tumor Cells, Cultured
MH  - Wnt Proteins
MH  - Zebrafish
MH  - *Zebrafish Proteins
PMC - PMC24445
EDAT- 1999/12/10 00:00
MHDA- 1999/12/10 00:01
CRDT- 1999/12/10 00:00
PHST- 1999/12/10 00:00 [pubmed]
PHST- 1999/12/10 00:01 [medline]
PHST- 1999/12/10 00:00 [entrez]
AID - 10.1073/pnas.96.25.14383 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Dec 7;96(25):14383-8. doi:
      10.1073/pnas.96.25.14383.