PMID- 9247199 OWN - NLM STAT- MEDLINE DCOM- 19971010 LR - 20220215 IS - 0021-9533 (Print) IS - 0021-9533 (Linking) VI - 110 ( Pt 14) DP - 1997 Jul TI - Cytosolic phospholipase A2 is activated by the hepatocyte growth factor receptor-kinase in Madin Darby canine kidney cells. PG - 1655-63 AB - The hepatocyte growth factor/scatter factor (HGF/SF) receptor which is a transmembrane protein encoded by the Met oncogene, possesses intrinsic tyrosine kinase activity which transduces the mitogenic, morphogenic and the scattering effect of HGF/SF. The pluripotent signal of HGF/SF is transduced through association of the Met receptor with various intracellular adaptors. Phosphorylation of cytosolic phospholipase A2 (cPLA2) is associated with activation of this molecule which in turn leads to arachidonic acid production followed by release of prostaglandins and related compounds exerting their roles onto cell proliferation, chemotaxis and vascular motility. Arachidonic acid and its metabolites were shown to be involved in processes like liver regeneration where growth factor receptors possessing tyrosine kinase activity are implicated. In this study we examined whether stimulation of the HGF/SF-receptor's tyrosine kinase activity would involve changes in the phosphorylation state and the activity of cPLA2 in MDCK cells, where HGF/SF is known to induce scattering responses rather than mitogenesis. The activated p145betaMET was shown to associate with and to phosphorylate cPLA2 on tyrosine residues, this leading to subsequent release of arachidonic acid. cPLA2 was also phosphorylated in serine residues and such a role has been so far assigned to the mitogen activated protein (MAP) kinase. Our data have also shown that MAP kinase is associated and phosphorylated on tyrosine by the activated p145betaMET. Immunodepletion of MAP kinase via electroporation of an anti-MAP kinase antibody, did not significantly decrease arachidonic acid release in HGF/SF-stimulated MDCK cells. It is therefore emerging that phosphorylation of cPLA2 on tyrosine by the HGF/SF receptor kinase is capable of triggering arachidonic acid release and that MAP kinase is contributing to full, but does not drive, the activity of cPLA2. The release of arachidonic acid by MDCK cells following HGF/SF stimulation is establishing this fatty acid and its metabolites as major components involved in the transduction of MET-driven signals and at the same time in the amplification of such signals. FAU - Skouteris, G G AU - Skouteris GG AD - Research Program of Applied Tumour Virology, Division of Virus-Host Interactions, Deutsches Krebsforschungszentrum, Heidelberg, Germany. FAU - Schroder, C H AU - Schroder CH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Cell Sci JT - Journal of cell science JID - 0052457 RN - 27YG812J1I (Arachidonic Acid) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-met) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases) RN - EC 3.1.1.32 (Phospholipases A) RN - EC 3.1.1.4 (Phospholipases A2) SB - IM MH - Animals MH - Arachidonic Acid/metabolism MH - Biological Transport/drug effects/physiology MH - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism MH - Cell Line MH - Cytosol/enzymology MH - Dogs MH - Hepatocyte Growth Factor/pharmacology MH - Kidney/*cytology MH - Phospholipases A/*metabolism MH - Phospholipases A2 MH - Phosphorylation MH - Proto-Oncogene Proteins c-met MH - Receptor Protein-Tyrosine Kinases/agonists/*metabolism MH - Signal Transduction/drug effects/*physiology EDAT- 1997/07/01 00:00 MHDA- 1997/07/01 00:01 CRDT- 1997/07/01 00:00 PHST- 1997/07/01 00:00 [pubmed] PHST- 1997/07/01 00:01 [medline] PHST- 1997/07/01 00:00 [entrez] AID - 10.1242/jcs.110.14.1655 [doi] PST - ppublish SO - J Cell Sci. 1997 Jul;110 ( Pt 14):1655-63. doi: 10.1242/jcs.110.14.1655.