PMID- 7499247 OWN - NLM STAT- MEDLINE DCOM- 19960117 LR - 20211203 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 270 IP - 46 DP - 1995 Nov 17 TI - Hepatocyte growth factor-induced scatter of Madin-Darby canine kidney cells requires phosphatidylinositol 3-kinase. PG - 27780-7 AB - Hepatocyte growth factor/scatter factor (HGF/SF) is a multifunctional cytokine that induces mitogenesis, motility, invasion, and morphogenesis of several epithelial and endothelial cell lines in culture. The receptor for HGF/SF has been identified as the Met tyrosine kinase. To investigate the signaling pathways that are involved in these events, we have generated chimeric receptors containing the extracellular domain of the colony-stimulating factor-1 (CSF-1) receptor fused to the transmembrane and intracellular domains of the Met receptor (MET). Madin-Darby canine kidney (MDCK) epithelial cells expressing the CSF-MET chimera dissociate and scatter in response to CSF-1. However, cells expressing a mutant CSF-MET receptor containing a phenylalanine substitution for tyrosine 1356 were unable to scatter or form branching tubules following stimulation with CSF-1. Tyrosine 1356 is essential for the recruitment of multiple substrates including the p85 subunit of PI3-kinase, phospholipase C gamma, and Grb2. In this study, we have investigated the role of PI3-kinase and a downstream target of PI3-kinase, pp70S6K, in the induction of MDCK cell scatter in response to HGF/SF. Our results demonstrate that following stimulation with HGF/SF, activation of PI3-kinase but not pp70S6K is essential for MDCK cell scatter. FAU - Royal, I AU - Royal I AD - Molecular Oncology Laboratory, Royal Victoria Hospital, Montreal, Quebec, Canada. FAU - Park, M AU - Park M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Androstadienes) RN - 0 (Cadherins) RN - 0 (Cell Adhesion Molecules) RN - 0 (Cytoskeletal Proteins) RN - 0 (Desmoplakins) RN - 0 (Enzyme Inhibitors) RN - 0 (Peptide Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - 81627-83-0 (Macrophage Colony-Stimulating Factor) RN - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor)) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-met) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) RN - EC 2.7.10.1 (Receptor, Macrophage Colony-Stimulating Factor) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.1 (Ribosomal Protein S6 Kinases) RN - XVA4O219QW (Wortmannin) SB - IM MH - Amino Acid Sequence MH - Androstadienes/pharmacology MH - Animals MH - Blotting, Western MH - Cadherins/analysis/metabolism MH - Cell Adhesion Molecules/analysis/metabolism MH - Cell Line MH - Cell Movement/drug effects/*physiology MH - Cytoskeletal Proteins/analysis/metabolism MH - Desmoplakins MH - Dogs MH - Enzyme Activation MH - Enzyme Inhibitors/pharmacology MH - Hepatocyte Growth Factor/*pharmacology MH - Kidney MH - Macrophage Colony-Stimulating Factor/pharmacology MH - Molecular Sequence Data MH - Peptide Fragments/chemistry MH - Phosphatidylinositol 3-Kinases MH - Phosphotransferases (Alcohol Group Acceptor)/*metabolism MH - Protein Serine-Threonine Kinases/isolation & purification/metabolism MH - Proto-Oncogene Proteins c-met MH - Receptor Protein-Tyrosine Kinases/biosynthesis/*physiology MH - Receptor, Macrophage Colony-Stimulating Factor/biosynthesis/metabolism MH - Recombinant Fusion Proteins/biosynthesis/metabolism MH - Ribosomal Protein S6 Kinases MH - Signal Transduction MH - Substrate Specificity MH - Wortmannin EDAT- 1995/11/17 00:00 MHDA- 1995/11/17 00:01 CRDT- 1995/11/17 00:00 PHST- 1995/11/17 00:00 [pubmed] PHST- 1995/11/17 00:01 [medline] PHST- 1995/11/17 00:00 [entrez] AID - S0021-9258(18)88021-8 [pii] AID - 10.1074/jbc.270.46.27780 [doi] PST - ppublish SO - J Biol Chem. 1995 Nov 17;270(46):27780-7. doi: 10.1074/jbc.270.46.27780.