PMID- 10559239 OWN - NLM STAT- MEDLINE DCOM- 19991214 LR - 20211203 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 274 IP - 47 DP - 1999 Nov 19 TI - Activation of rat frizzled-1 promotes Wnt signaling and differentiation of mouse F9 teratocarcinoma cells via pathways that require Galpha(q) and Galpha(o) function. PG - 33539-44 AB - The frizzled gene family of putative Wnt receptors encodes proteins that have a seven transmembrane-spanning motif characteristic of G-protein-linked receptors, although no loss-of-function studies have demonstrated a requirement for G-proteins for Wnt signaling by the gene product of frizzled-1. Medium conditioned by mouse F9 teratocarcinoma stem cells stably transfected to express either Xenopus Wnt-5a or Wnt-8 was used to test primitive endoderm formation of F9 stem cells. F9 stem cells expressing the rat Frizzled-1 receptors demonstrated endoderm formation in response to conditioned medium containing Wnt-8 but not to medium containing Wnt-5a. Primitive endoderm formation stimulated by Wnt-8 acting on the rat Frizzled-1 receptor was blocked by treatment with pertussis toxin by depletion of either Galpha(o) or Galpha(q) via antisense oligodeoxynucleotides, as well as by inhibitors of protein kinase C (bisindoylmaleimide) and of mitogen-activated protein kinase kinase (PD98059). Our results demonstrate the requirement for G-protein subunits Galpha(o) (a pertussis toxin substrate) and Galpha(q) for signaling by Frizzled-1, and an obligate role for the protein kinase C (likely mediated through stimulation of Galpha(q)) and mitogen-activated protein kinase network at the level of mitogen-activated protein kinase kinase. FAU - Liu, T AU - Liu T AD - Department of Pharmacology, State University of New York, Stony Brook, New York 11794-8651, USA. FAU - Liu, X AU - Liu X FAU - Wang, H y AU - Wang Hy FAU - Moon, R T AU - Moon RT FAU - Malbon, C C AU - Malbon CC LA - eng PT - Journal Article PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Culture Media, Conditioned) RN - 0 (Enzyme Inhibitors) RN - 0 (FZD1 protein, Xenopus) RN - 0 (Frizzled Receptors) RN - 0 (Fzd1 protein, mouse) RN - 0 (Phosphoinositide-3 Kinase Inhibitors) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Receptors, G-Protein-Coupled) RN - 0 (Receptors, Neurotransmitter) RN - 0 (Virulence Factors, Bordetella) RN - 0 (Wnt Proteins) RN - 0 (Xenopus Proteins) RN - 0 (Zebrafish Proteins) RN - 149748-09-4 (Fzd1 protein, rat) RN - EC 2.4.2.31 (Pertussis Toxin) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.13 (Protein Kinase C) RN - EC 2.7.11.25 (MAP Kinase Kinase Kinase 1) RN - EC 2.7.11.25 (MAP Kinase Kinase Kinases) RN - EC 2.7.11.25 (Map3k1 protein, mouse) RN - EC 3.1.4.35 (3',5'-Cyclic-GMP Phosphodiesterases) RN - EC 3.6.1.- (GTP-Binding Proteins) SB - IM MH - 3',5'-Cyclic-GMP Phosphodiesterases/antagonists & inhibitors MH - Animals MH - Clone Cells MH - Culture Media, Conditioned MH - Enzyme Inhibitors/pharmacology MH - Fluorescent Antibody Technique, Indirect MH - Frizzled Receptors MH - GTP-Binding Proteins/antagonists & inhibitors/*metabolism MH - *MAP Kinase Kinase Kinase 1 MH - MAP Kinase Kinase Kinases/antagonists & inhibitors MH - Mice MH - Pertussis Toxin MH - Phosphoinositide-3 Kinase Inhibitors MH - Protein Kinase C/antagonists & inhibitors MH - *Protein Serine-Threonine Kinases MH - Proto-Oncogene Proteins/*metabolism MH - Rats MH - Receptors, G-Protein-Coupled MH - Receptors, Neurotransmitter/*metabolism MH - *Signal Transduction MH - Teratocarcinoma/*metabolism/pathology MH - Tumor Cells, Cultured MH - Virulence Factors, Bordetella/pharmacology MH - Wnt Proteins MH - *Xenopus Proteins MH - *Zebrafish Proteins EDAT- 1999/11/24 00:00 MHDA- 1999/11/24 00:01 CRDT- 1999/11/24 00:00 PHST- 1999/11/24 00:00 [pubmed] PHST- 1999/11/24 00:01 [medline] PHST- 1999/11/24 00:00 [entrez] AID - 10.1074/jbc.274.47.33539 [doi] AID - S0021-9258(17)46497-0 [pii] PST - ppublish SO - J Biol Chem. 1999 Nov 19;274(47):33539-44. doi: 10.1074/jbc.274.47.33539.