The Raf-1 kinase associates with vimentin kinases and regulates the structure of vimentin filaments

Autor(en)

Petra Janosch, Arnd Kieser, Manfred Eulitz, Josip Lovric, Guido Sauer, Manuela Reichert, Fotini Gounari, Dirk Büscher, Manuela Baccarini, Harald Mischak, Walter Kolch

Abstrakt

Using immobilized GST-Raf-1 as bait, we have isolated the intermediate filament protein vimentin as a Raf-1-associated protein. Vimentin coimmunoprecipitated and colocalized with Raf-1 in fibroblasts. Vimentin was not a Raf-1 substrate, but was phosphorylated by Raf-1-associated vimentin kinases. We provide evidence for at least two Raf-1-associated vimentin kinases and identified one as casein kinase 2. They are regulated by Raf-1, since the activation status of Raf-1 correlated with the phosphorylation of vimentin. Vimentin phosphorylation by Raf-1 preparations interfered with its polymerization in vitro. A subset of tryptic vimentin phosphopeptides induced by Raf-1 in vitro matched the vimentin phosphopeptides isolated from v-raf-transfected cells labeled with orthophosphoric acid, indicating that Raf-1 also induces vimentin phosphorylation in intact cells. In NIH 3T3 fibroblasts, the selective activation of an estrotgen-regulated Raf-1 mutant induced a rearrangement and depolymerization of the reticular vimentin scaffold similar to the changes elicited by serum treatment. The rearrangement of the vimentin network occurred independently of the MEK/ERK pathway. These data identify a new branch point in Raf-1 signaling, which links Raf-1 to changes in the cytoskeletal architecture.

Organisation(en)

Externe Organisation(en)

BICR - Beatson Institute for Cancer Research, Helmholtz-Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt, Université de Lausanne, The Salk Institute for Biological Studies, Dana-Farber Cancer Institute, Medizinische Hochschule Hannover (MHH)

Journal

The FASEB Journal

Band

14

Seiten

2008-2021

Anzahl der Seiten

14

ISSN

0892-6638

DOI

https://doi.org/10.1096/fj.99-0883com

Publikationsdatum

2000

Peer-reviewed

Ja

ÖFOS 2012

1060 Biologie

Link zum Portal

https://ucrisportal.univie.ac.at/de/publications/the-raf1-kinase-associates-with-vimentin-kinases-and-regulates-the-structure-of-vimentin-filaments(d80f4e85-0000-49db-a870-caac23045e25).html