ERK and beyond: Insights from B-Raf and Raf-1 conditional knockouts

Autor(en)

Gergana Galabova-Kovacs, Andrea Kolbus, Dana Matzen, Katrin Meissl, Daniela Piazzolla, Cristina Rubiolo, Manuela Baccarini

Abstrakt

The Raf/MEK/ERK cascade is a highly conserved signal transduction module whose activation reportedly results in a plethora of physiological outcomes. Depending on the cell type or the stimulus used, the pathway has been implicated in proliferation, differentiation, survival, and migration. Their wide range of activities renders the component of the Raf/MEK/ERK pathway prime candidates for molecule-targeted therapies, in particular, but not exclusively, in the context of cancer. Ras, Raf and MEK inhibitors have been developed, and some of them are in advanced clinical trials. Somewhat surprising in view of all this interest, our understanding of the fundamental biology of the ERK pathway in vivo is still scanty. Its investigation has been hampered by the fact that conventional targeting of many of these genes results in embryonic lethality. Recently, we and others have generated mouse strains that allow the conditional ablation of the genes coding for Raf-1, B-Raf and MEK-1. We are using these tools to identify the essential biological functions of these kinases, and to understand how the ERK pathway is wired in vivo. Here, we discuss some of the surprises yielded by the analysis of the role of B-Raf and Raf-1 and of their downstream effectors. Œ2006 Landes Bioscience.

Organisation(en)

Externe Organisation(en)

Medizinische Universität Wien, Cell Med Research GmbH

Journal

Cell Cycle

Band

5

Seiten

1514-1518

Anzahl der Seiten

5

ISSN

1538-4101

DOI

https://doi.org/10.4161/cc.5.14.2981

Publikationsdatum

2006

Peer-reviewed

Ja

ÖFOS 2012

106001 Allgemeine Biologie

Sustainable Development Goals

SDG 3 – Gesundheit und Wohlergehen

Link zum Portal

https://ucrisportal.univie.ac.at/de/publications/erk-and-beyond-insights-from-braf-and-raf1-conditional-knockouts(cdf8ceda-4755-4d09-8446-8006ff1269dd).html