PubMed Journals: J Biol Chem
Source: PMID: 10318869
⇦ ⇨ J Biol Chem. 1999 May 14;274(20):14434-43.
MAPKAP kinase 2 phosphorylates
serum response factor in vitro and in
Heidenreich O(1), Neininger A, Schratt G,
Zinck R, Cahill MA, Engel K, Kotlyarov A,
Kraft R, Kostka S, Gaestel M, Nordheim A.
(1) Institut für Zellbiologie, Abteilung
Molekularbiologie, Universität Tübingen,
D-72076 Tübingen, Germany.
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.
PMID: 10318869 [Indexed for MEDLINE]