Protein phosphatase 2A potentiates activity of promoters containing AP-1-binding elements.
The involvement of serine/threonine protein phosphatases in signaling pathways which modulate the activity of the transcription factor AP-1 was examined. Purified protein phosphatase types 1 (PP1) and 2A (PP2A) were microinjected into cell lines containing stably transfected lacZ marker genes under the control of an enhancer recognized by AP-1. Microinjection of PP2A potentiated serum-stimulated beta-galactosidase expression from the AP-1-regulated promoter. Similarly, transient expression of the PP2A catalytic subunit with c-Jun resulted in a synergistic transactivation of an AP-1-regulated reporter gene. PP2A, but not PP1, potentiated serum-induced c-Jun expression, which has been previously shown to be autoregulated by AP-1 itself. Consistent with these results, PP2A dephosphorylated c-Jun on negative regulatory sites in vitro, suggesting one possible direct mechanism for the effects of PP2A on AP-1 activity. Microinjection of PP2A had no effect on cyclic AMP (cAMP)-induced expression of a reporter gene containing a cAMP-regulated promoter, while PP1 injection abolished cAMP-induced gene expression. Taken together, these results suggest a specific role for PP2A in signal transduction pathways that regulate AP-1 activity and c-Jun expression.
Department of Pharmacology, University of California, San Diego, La Jolla 92093-0636.
A S
AS
Alberts
T
T
Deng
A
A
Lin
J L
JL
Meinkoth
A
A
Schönthal
M C
MC
Mumby
M
M
Karin
J R
JR
Feramisco
D000818:Animals; D001483:Base Sequence; D002417:Cattle; D005786:Gene Expression Regulation; D066298:In Vitro Techniques; D008845:Microinjections; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D010749:Phosphoprotein Phosphatases / Q000502:physiology*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D054648:Protein Phosphatase 2; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D015533:Transcriptional Activation
D009838:Oligodeoxyribonucleotides; D016755:Proto-Oncogene Proteins c-jun; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2