Role of serine/threonine protein kinases in the induction of JE, a platelet-derived growth factor inducible gene.

Platelet-derived growth factor (PDGF) and serum both stimulate the transcription of the mouse early response gene, JE. JE and its human homolog, macrophage chemotactic protein-1 (MCP-1), encode potent monocyte chemotactic factors. JE/MCP-1 is a member of the chemokine superfamily of small inducible genes whose products are multifaceted mediators of inflammatory and immune responses. We now report evidence that the serine/threonine kinase inhibitors H7 and H8 but not HA1004, W-7, and ML-7 inhibit the transcriptional induction of the JE gene by serum whereas the phosphatase inhibitor, okadaic acid, increases JE expression. Downregulation of protein kinase C by prior exposure to TPA does not inhibit the induction of JE by serum, nor does it affect the inhibition of JE induction by H7. These results suggest that one or more serine/threonine kinases may be important in the signal transduction mechanism that leads to the induction of the JE gene.