MEK is a negative regulator of Stat5b in PDGF-stimulated cells.
In this study we show that platelet-derived growth factor (PDGF)-induced DNA binding as well as transcriptional activation of Stat5b are markedly increased by inhibition of the MAP (mitogen-activated protein) kinase kinase MEK. In addition to the previously demonstrated tyrosine phosphorylation, we show that serine and threonine phosphorylation of Stat5b is increased in response to PDGF stimulation. However, inhibition of MEK had no effect on the phosphorylation level of Stat5b or on the nuclear translocation of Stat5b. These observations indicate that MEK is a negative modulator of PDGF-induced Stat5b activation through a mechanism not involving direct phosphorylation of Stat5b.
Valgeirsdóttir
S
S
Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
Ruusala
A
A
Heldin
C H
CH
D000818:Animals; D000077214:Becaplermin; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D048369:MAP Kinase Kinase 1; D008894:Milk Proteins; D019950:Mitogen-Activated Protein Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D019606:Phosphoamino Acids / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000032:analysis; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D013552:Swine; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D005419:Flavonoids; D008894:Milk Proteins; D019606:Phosphoamino Acids; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D000077214:Becaplermin; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one