MAPKAP kinase 2 phosphorylates serum response factor in vitro and in vivo

Several growth factor- and calcium-regulated kinases such as pp90(rsk) or C aM kinase TV can phosphorylate the transcription factor serum response fact or (SRF) at serine 103 (Ser-103). However, it is unknown whether stress-reg ulated kinases can also phosphorylate SRF. We show that treatment of cells with anisomycin, arsenite, sodium fluoride, or tetrafluoroaluminate induces phosphorylation of SRF at Ser-103 in both HeLa and NIH3T3 cells. This phos phorylation is dependent on the kinase p38/SAPK2 and correlates with the ac tivation of MAPKAP kinase 2 (MK2). MK2 phosphorylates SRF in vitro at Ser-1 03 with similar efficiency as the small heat shock protein Hsp25 and signif icantly better than CREB, Comparison of wild type murine fibroblasts with t hose derived from MK2-deficient mice (Mk(-/-)) reveals MK2 as the major SRF kinase induced by arsenite. These results demonstrate that SRF is targeted by several signal transduction pathways within cells and establishes SRF a s a nuclear target for MAPKAP kinase 2.