MAPKAP Kinase 2 Phosphorylates Serum Response Factor in Vitro and in Vivo*

O. Heidenreich,A. Neininger,G. Schratt,R. Zinck,M. Cahill,K. Engel,A. Kotlyarov,R. Kraft,S. Kostka,M. Gaestel,A. Nordheim

Published 1999 in Journal of Biological Chemistry

ABSTRACT

Several growth factor- and calcium-regulated kinases such as pp90 rsk or CaM kinase IV can phosphorylate the transcription factor serum response factor (SRF) at serine 103 (Ser-103). However, it is unknown whether stress-regulated 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 phosphorylation is dependent on the kinase p38/SAPK2 and correlates with the activation of MAPKAP kinase 2 (MK2). MK2 phosphorylates SRFin vitro at Ser-103 with similar efficiency as the small heat shock protein Hsp25 and significantly better than CREB. Comparison of wild type murine fibroblasts with those 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 as a nuclear target for MAPKAP kinase 2.

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