Published online May 29, 2007
doi:10.1083/jcb.200703174
The Journal of Cell Biology, Vol. 177, No. 5, 795-807
The Rockefeller University Press, 0021-9525 $30.00
© 2007 Wöll et al.
p38 MAPK-dependent shaping of the keratin cytoskeleton in cultured cells
Stefan Wöll,
Reinhard Windoffer, and
Rudolf E. Leube
Department of Anatomy and Cell Biology, Johannes Gutenberg University, 55128 Mainz, Germany
Correspondence to Rudolf Leube: leube{at}uni-mainz.de
Plasticity of the resilient keratin intermediate filament cytoskeleton is an important prerequisite for epithelial tissue homeostasis. Here, the contribution of stress-activated p38 MAPK to keratin network organization was examined in cultured cells. It was observed that phosphorylated p38 colocalized with keratin granules that were rapidly formed in response to orthovanadate. The same p38p recruitment was noted during mitosis, in various stress situations and in cells producing mutant keratins. In all these situations keratin 8 became phosphorylated on S73, a well-known p38 target site. To demonstrate that p38-dependent keratin phosphorylation determines keratin organization, p38 activity was pharmacologically and genetically modulated: up-regulation induced keratin granule formation, whereas down-regulation prevented keratin filament network disassembly. Furthermore, transient p38 inhibition also inhibited keratin filament precursor formation and mutant keratin granule dissolution. Collectively, the rapid and reversible effects of p38 activity on keratin phosphorylation and organization in diverse physiological, stress, and pathological situations identify p38-dependent signalling as a major intermediate filament–regulating pathway.
Abbreviations used in this paper: IF, intermediate filament; K8, keratin 8; KF, keratin filament; OV, orthovanadate; p38p, phosphorylated p38.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
