Raf-1 regulates Rho signaling and cell migration

Autor(en)

Karin Ehrenreiter, Daniela Piazzolla, Vanishree Velamoor, Izabela Sobczak, John-Victor Small, Junji Takeda, Thomas Leung, Manuela Baccarini

Abstrakt

Raf kinases relay signals inducing proliferation, differentiation, and survival. The Raf-1 isoform has been extensively studied as the upstream kinase linking Ras activation to the MEK/ERK module. Recently, however, genetic experiments have shown that Raf-1 plays an essential role in counteracting apoptosis, and that it does so independently of its ability to activate MEK. By conditional gene ablation, we now show that Raf-1 is required for normal wound healing in vivo and for the migration of keratinocytes and fibroblasts in vitro. Raf-1-deficient cells show a symmetric, contracted appearance, characterized by cortical actin bundles and by a disordered vimentin cytoskeleton. These defects are due to the hyperactivity and incorrect localization of the Rho-effector Rok-a to the plasma membrane. Raf-1 physically associates with Rok-a in wild-type (WT) cells, and reintroduction of either WT or kinase-dead Raf-1 in knockout fibroblasts rescues their defects in shape and migration. Thus, Raf-1 plays an essential, kinase-independent function as a spatial regulator of Rho downstream signaling during migration.

Organisation(en)

Department für Biochemie und Zellbiologie

Externe Organisation(en)

Max F. Perutz Laboratories GmbH (MFPL), Osaka University, Institute of Molecular and Cell Biology (IMCB)

Journal

The Journal of Cell Biology (JCB)

Band

168

Seiten

955-964

Anzahl der Seiten

10

ISSN

0021-9525

Publikationsdatum

2005

Peer-reviewed

Ja

ÖFOS 2012

1060 Biologie

Link zum Portal

https://ucrisportal.univie.ac.at/de/publications/raf1-regulates-rho-signaling-and-cell-migration(30c24341-c3f1-4039-9c0a-f5b4ea1af0d4).html