Schönthal A, Tsukitani Y, Feramisco J R
UCSD Cancer Center, University of California, La Jolla 92093.
Oncogene. 1991 Mar;6(3):423-30.
Phosphorylation events are major regulatory mechanisms of signal transduction pathways that control cell growth and differentiation. We analyzed the potential contribution of serine/threonine specific protein phosphatases to the regulation of the c-fos gene, a proto-oncogene that is involved in the regulation of cell growth and differentiation. By use of okadaic acid, an inhibitor of protein phosphatases 1 and 2A, we present evidence that expression of the c-fos gene is regulated by serine/threonine specific protein phosphatases. This control is exerted on the transcriptional as well as the post-transcriptional level. The results suggest that dephosphorylation of regulatory phosphoproteins is an important mechanism for the down-regulation of c-fos promoter activity and the rapid degradation of c-fos mRNA. Examination of two protein kinase pathways that are known to regulate c-fos expression indicated that okadaic acid acted synergistically with protein kinase C, but not with protein kinase A. Since inhibition of serine/threonine specific phosphatases increases proto-oncogene expression, these experiments further strengthen the view that certain protein phosphatases may act as negative regulators of cell growth.
