Oligomerization activates c-Raf-1 through a Ras-dependent mechanism
- 1 September 1996
- journal article
- Published by Springer Nature in Nature
- Vol. 383 (6596), 181-185
- https://doi.org/10.1038/383181a0
Abstract
The c-Raf-1 proto-oncoprotein is a Ras-GTP-regulated protein kinase that associates in situ with 14-3-3 proteins, which are naturally dimeric. In COS cells, recombinant Raf is found in oligomeric assemblies. To examine whether induced oligomerization can alter Raf kinase activity, sequences encoding the FK506-binding protein FKBP12 were fused to the amino terminus of c-Raf-1, introducing a binding site for FK506. Oligomerization of recombinant FKBP-Raf in situ, induced by the addition of the dimeric FK506 derivative FK1012A, activated Raf kinase activity at least half as well as epidermal growth factor (EGF). As with EGF, activation of FKBP-Raf by FK1012A is entirely Ras-GTP dependent. Thus oligomerization of Raf per se promotes Raf activation through a Ras-dependent mechanism.Keywords
This publication has 21 references indexed in Scilit:
- Identification of the 14.3.3 ζ Domains Important for Self-association and Raf BindingPublished by Elsevier ,1995
- Crystal structure of the zeta isoform of the 14-3-3 proteinNature, 1995
- Structure of a 14-3-3 protein and implications for coordination of multiple signalling pathwaysNature, 1995
- Binding of 14-3-3 Proteins to the Protein Kinase Raf and Effects on Its ActivationScience, 1994
- Raf meets Ras: completing the framework of a signal transduction pathwayTrends in Biochemical Sciences, 1994
- Proteins regulating Ras and its relativesNature, 1993
- Controlling Signal Transduction with Synthetic LigandsScience, 1993
- Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1Nature, 1993
- Mammalian Ras interacts directly with the serine/threonine kinase rafCell, 1993
- Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexesCell, 1991