Expression of I2PP2A, an inhibitor of protein phosphatase 2A, induces c-Jun and AP-1 activity.
Transient expression of I2PP2A, a potent inhibitor of protein phosphatase 2A (PP2A), in HEK-293 cells increased the concentration and DNA binding of the proto-oncogene c-Jun. In contrast, expression of the catalytic subunit of PP2A (PP2AC) markedly decreased the concentration and DNA binding of c-Jun. Expression of I2PP2A also increased the transcriptional activity of activator protein-1, and this effect was diminished in a dose-dependent manner by expression of PP2AC. Densitometric analysis following Western blotting of extracts with antibodies specific for phospho-Ser63 and Ser73 suggests that the effects of I2PP2A and PP2AC expression might be mediated, in part, by changes in the phosphorylation of c-Jun at Ser63. The results indicate that I2PP2A elicits effects that are consistent with it acting as an inhibitor of PP2A in intact cells, and suggest that PP2A might exhibit site selectivity with respect to c-Jun phosphorylation.
Department of Cellular and Molecular Physiology H166, The Pennsylvania State University College of Medicine, Milton S. Hershey Medical Centre, P.O. Box 850, Hershey, PA 17033, USA.
S W
SW
Al-Murrani
J R
JR
Woodgett
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Z
Damuni
D002460:Cell Line; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation; D016758:Genes, jun; D056488:Histone Chaperones; D006801:Humans; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000235:genetics*; D054648:Protein Phosphatase 2; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D015398:Signal Transduction / Q000235:genetics*; D018808:Transcription Factor AP-1 / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors; D014162:Transfection
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D056488:Histone Chaperones; C000715470:MAS1 protein, human; D011506:Proteins; D000090063:Proto-Oncogene Mas; C513473:SET protein, human; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2