ABSTRACT
This chapter discusses what is known to date of the means by which activator protein (AP-1) is constitutively activated by specific oncogenes and, by extrapolation, how AP-1 activity is potentiated in response to growth factors and mitogenic stimuli in untransformed cells. The function of AP-1 is controlled in part through posttranslational modification, principally phosphorylation, of its two components, Jun and Fos. The chapter describes two recurrent themes, therefore, phosphorylation of transcription factors by protein kinases and, to an extent reduced almost to inference, their dephosphorylation by protein phosphatases. Overexpression of the wild-type receptor-like protein tyrosine phosphatase in embryonal fibroblasts results in chronic dephosphorylation of the negative regulatory Tyr527 of pp60src. Phosphatases are essential for regulation of intracellular functions by phosphorylation. The activity of AP-1, the nuclear transcription factor that comprises the c-fos and c-jun gene products, is subject to modulation by phosphorylation at various levels.
