ERK pathway positively regulates the expression of Sprouty genes.
Sprouty was originally identified as an inhibitor of Drosophila development-associated receptor tyrosine kinase (RTK) signaling. Although RTK signaling has been shown to induce Sprouty gene expression, the precise induction pathway downstream of RTK remains unclear. As RTK signaling pathway includes activation of extracellular signal-regulated kinases (ERKs), we have examined a correlation between activation of ERKs and induction of Sprouty gene expression. All reagents which induce the activation of ERKs induce Sprouty gene expression; these agents include not only growth factors which bind to RTK but also phorbol 12-myristate-13-acetate and active Raf-1 kinase. Furthermore, the Sprouty gene expression induced by all those agents is totally suppressed when the cells are pretreated with specific inhibitors of ERK kinase (MEK). Human tumor cells which exhibit constitutive activation of ERKs show elevated expression of Sprouty genes, which is abolished by treatment of these cells with MEK inhibitors. All these findings clearly indicate that Sprouty gene expression is positively regulated by the ERK pathway downstream of RTK.
Ozaki
K
K
Laboratory of Cell Regulation, School of Pharmaceutical Sciences, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki, 852-8521, Japan. kohnom@net.nagasaki-u.ac.jp
Kadomoto
R
R
Asato
K
K
Tanimura
S
S
Itoh
N
N
Kohno
M
M
D000818:Animals; D002460:Cell Line; D029721:Drosophila Proteins; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005246:Feedback / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D019476:Insect Proteins / Q000235:genetics* / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008934:Mitogens / Q000494:pharmacology; D009369:Neoplasms / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases
D029721:Drosophila Proteins; D004791:Enzyme Inhibitors; D019476:Insect Proteins; D008565:Membrane Proteins; D008934:Mitogens; D000081082:Phosphoinositide-3 Kinase Inhibitors; C110486:sty protein, Drosophila; D016222:Fibroblast Growth Factor 2; D019908:Proto-Oncogene Proteins c-raf; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases