Unexpected suppression of alpha-smooth muscle actin, the activation marker of mesangial cells, by pp60v-src tyrosine kinase.
Cultured mesangial cells constitutively express alpha-smooth muscle actin (alpha-SMA), a marker of cellular activation. We unexpectedly found that tyrosine kinase pp60v-src, a known activator for a wide range of signalling cascades, suppressed the alpha-SMA expression in mesangial cells. The present study was conducted to elucidate molecular events involved in this phenomenon. Transfection with a reporter plasmid revealed that the serum response element (SRE), the cis-element required for alpha-SMA expression, was constitutively active in mesangial cells. When mesangial cells were transfected with pp60v-src, activity of both SRE and the alpha-SMA promoter was down-regulated. This was associated with depressed levels of phosphorylated extracellular signal-regulated kinases (ERKs), but not c-Jun N-terminal kinase. Selective inhibition of ERKs by PD098059 abrogated constitutive SRE activity, leading to suppressed alpha-SMA expression. These results uncovered a novel potential of pp60v-src for suppression of alpha-SMA via intervention in the ERK-SRE signalling pathway.
Ishikawa
Y
Y
Department of Medicine, University College London Medical School, United Kingdom.
Kitamura
M
M
D000199:Actins / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D008297:Male; D009687:Nuclear Proteins / Q000378:metabolism; D015688:Oncogene Protein pp60(v-src) / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012045:Regulatory Sequences, Nucleic Acid; D026362:Serum Response Factor; D015398:Signal Transduction
D000199:Actins; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D026362:Serum Response Factor; D015688:Oncogene Protein pp60(v-src); D017871:Calcium-Calmodulin-Dependent Protein Kinases