PMID- 10318869 OWN - NLM STAT- MEDLINE DCOM- 19990617 LR - 20210209 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 274 IP - 20 DP - 1999 May 14 TI - MAPKAP kinase 2 phosphorylates serum response factor in vitro and in vivo. PG - 14434-43 AB - 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 SRF in 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. FAU - Heidenreich, O AU - Heidenreich O AD - Institut fur Zellbiologie, Abteilung Molekularbiologie, Universitat Tubingen, D-72076 Tubingen, Germany. FAU - Neininger, A AU - Neininger A FAU - Schratt, G AU - Schratt G FAU - Zinck, R AU - Zinck R FAU - Cahill, M A AU - Cahill MA FAU - Engel, K AU - Engel K FAU - Kotlyarov, A AU - Kotlyarov A FAU - Kraft, R AU - Kraft R FAU - Kostka, S AU - Kostka S FAU - Gaestel, M AU - Gaestel M FAU - Nordheim, A AU - Nordheim A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Arsenites) RN - 0 (DNA-Binding Proteins) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Nuclear Proteins) RN - 0 (Serum Response Factor) RN - 0 (Teratogens) RN - 452VLY9402 (Serine) RN - EC 2.7.1.- (MAP-kinase-activated kinase 2) RN - EC 2.7.11.1 (Protein-Serine-Threonine Kinases) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - N5509X556J (arsenite) SB - IM MH - 3T3 Cells MH - Animals MH - Arsenites/pharmacology MH - Calcium-Calmodulin-Dependent Protein Kinases/metabolism MH - DNA-Binding Proteins/*metabolism MH - Fibroblasts/drug effects/metabolism MH - HeLa Cells MH - Humans MH - Intracellular Signaling Peptides and Proteins MH - Mice MH - *Mitogen-Activated Protein Kinases MH - Nuclear Proteins/*metabolism MH - Phosphorylation MH - Protein-Serine-Threonine Kinases/*metabolism MH - Serine/metabolism MH - Serum Response Factor MH - Signal Transduction/drug effects MH - Teratogens/pharmacology MH - p38 Mitogen-Activated Protein Kinases EDAT- 1999/05/13 00:00 MHDA- 1999/05/13 00:01 CRDT- 1999/05/13 00:00 PHST- 1999/05/13 00:00 [pubmed] PHST- 1999/05/13 00:01 [medline] PHST- 1999/05/13 00:00 [entrez] AID - 10.1074/jbc.274.20.14434 [doi] AID - S0021-9258(19)73321-3 [pii] PST - ppublish SO - J Biol Chem. 1999 May 14;274(20):14434-43. doi: 10.1074/jbc.274.20.14434.