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ZFIN ID: ZDB-PUB-150826-1
The Kinase Activity-deficient Isoform of the Protein Araf Antagonizes Ras/Mitogen-activated Protein Kinase (Ras/MAPK) Signaling in the Zebrafish Embryo
Xiong, C., Liu, X., Meng, A.
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.
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.