PUBLICATION
The Kinase Activity-deficient Isoform of the Protein Araf Antagonizes Ras/Mitogen-activated Protein Kinase (Ras/MAPK) Signaling in the Zebrafish Embryo
- Authors
- Xiong, C., Liu, X., Meng, A.
- ID
- ZDB-PUB-150826-1
- Date
- 2015
- Source
- The Journal of biological chemistry 290(42): 25512-21 (Journal)
- Registered Authors
- Meng, Anming, Xiong, Cong
- Keywords
- Araf, Ras protein, embryo, fibroblast growth factor (FGF), mesoderm, mitogen-activated protein kinase (MAPK), patterning, transcript variant, zebrafish
- MeSH Terms
-
- Animals
- Cell Line
- Embryonic Development
- Fibroblast Growth Factors/metabolism
- Humans
- Isoenzymes/genetics
- Isoenzymes/metabolism*
- Mitogen-Activated Protein Kinases/genetics
- Mitogen-Activated Protein Kinases/metabolism*
- Proto-Oncogene Proteins c-raf/genetics
- Proto-Oncogene Proteins c-raf/metabolism*
- Signal Transduction*
- Zebrafish/embryology*
- PubMed
- 26306042 Full text @ J. Biol. Chem.
Citation
Xiong, C., Liu, X., Meng, A. (2015) The Kinase Activity-deficient Isoform of the Protein Araf Antagonizes Ras/Mitogen-activated Protein Kinase (Ras/MAPK) Signaling in the Zebrafish Embryo. The Journal of biological chemistry. 290(42):25512-21.
Abstract
Raf kinases are important components of the Ras-Raf-Mek-Erk pathway and also cross-talk with other signaling pathways. Araf kinase has been demonstrated to inhibit TGF-β/Smad2 signaling by directly phosphorylating and accelerating degradation of activated Smad2. In this study, we show that the araf gene expresses in zebrafish embryos to produce a shorter transcript variant, araf-tv2, in addition to the full length variant araf-tv1. araf-tv2 is predicted to encode a C-terminally truncated peptide without the kinase activity domain. Araf-tv2 can physically associate with Araf-tv1 but does not antagonize the inhibitory effect of Araf-tv1 on TGF-β/Smad2 signaling. Instead, Araf-tv2 interacts strongly with Kras and Nras, ultimately blocking MAPK activation by these Ras proteins. In zebrafish embryos, overexpression of araf-tv2 is sufficient to inhibit Fgf/Ras-promoted Erk activation, mesodermal induction, dorsal development and neuroectodermal posteriorization. Therefore, different isoforms of Araf may participate in similar developmental processes but by regulating different signaling pathways.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping