MAPKAP kinase-2 is a primary response gene induced by depolarization in PC12 cells and in brain

Using a combination of targeted differential display for induced protein kinases and differential library screening, we identified mitogen-activated protein kinase activated protein kinase 2 (MAPKAPK2), as a primary response gene whose transcription is stimulated by membrane depolarization and by forskolin in rat PC12 pheochromocytoma cells. MAPKAPK3 was neither induced nor repressed by similar treatments. The increase in MAPKAPK2 mRNA is preceded by an increase in a MAPKAPK2 intron-containing RNA precursor, indicating that the increase in message is due at least in part to increased transcription. The open reading frame of full-length rat MAPKAPK2 cDNA is 99% identical to mouse MAPKAPK2 and 92% identical to human MAPKAPK2. The human MAPKAPK2 predicted protein contains 14 additional amino acids in the proline-rich N-terminal domain, when compared to murine and rat MAPKAPK2 predicted proteins. The MAPKAPK2 form found in PC12 cells corresponds to variant 2 in the human; this ortholog carries a nuclear translocation signal near its C-terminus. MAPKAPK2 message is also induced in the dentate gyrus, CA1, and CA3 of the rat hippocampus between 2-4 hr after the onset of kainic acid-induced seizures.