RRC ID 58476
Author Vega-Cuesta P, Ruiz-Gómez A, Molnar C, Organista MF, Resnik-Docampo M, Falo-Sanjuan J, López-Varea A, de Celis JF.
Title Ras2, the TC21/R-Ras2 Drosophila homologue, contributes to insulin signalling but is not required for organism viability.
Journal Dev Biol
Abstract Ras1 (Ras85D) and Ras2 (Ras64B) are the Drosophila orthologs of human H-Ras/N-Ras/K-Ras and R-Ras1-3 genes, respectively. The function of Ras1 has been thoroughly characterised during Drosophila embryonic and imaginal development, and it is associated with coupling activated trans-membrane receptors with tyrosine kinase activity to their downstream effectors. In this capacity, Ras1 binds and is required for the activation of Raf. Ras1 can also interact with PI3K, and it is needed to achieve maximal levels of PI3K signalling in specific cellular settings. In contrast, the function of the unique Drosophila R-Ras member (Ras2/Ras64B), which is more closely related to vertebrate R-Ras2/TC21, has been only studied through the use of constitutively activated forms of the protein. This pioneering work identified a variety of phenotypes that were related to those displayed by Ras1, suggesting that Ras1 and Ras2 might have overlapping activities. Here we find that Ras2 can interact with PI3K and Raf and activate their downstream effectors Akt and Erk. However, and in contrast to mutants in Ras1, which are lethal, null alleles of Ras2 are viable in homozygosis and only show a phenotype of reduced wing size and extended life span that might be related to reduced Insulin receptor signalling.
Volume 461(2)
Pages 172-183
Published 2020-5-15
DOI 10.1016/j.ydbio.2020.02.009
PII S0012-1606(20)30060-9
PMID 32061885
MeSH Amino Acid Sequence Animals CRISPR-Cas Systems Drosophila Proteins / genetics Drosophila Proteins / physiology* Drosophila melanogaster / genetics Drosophila melanogaster / physiology* ErbB Receptors Female Gene Editing Genetic Association Studies Insulin / physiology* Longevity / genetics Male Membrane Proteins / genetics Membrane Proteins / physiology* Phosphatidylinositol 3-Kinases / genetics Phosphatidylinositol 3-Kinases / metabolism Protein Interaction Mapping Proto-Oncogene Proteins c-raf / genetics Proto-Oncogene Proteins c-raf / physiology Receptor Protein-Tyrosine Kinases / physiology Receptors, Invertebrate Peptide Recombinant Fusion Proteins / metabolism Sequence Alignment Sequence Homology, Amino Acid Signal Transduction / physiology Wings, Animal / growth & development Wings, Animal / ultrastructure ras Proteins / genetics ras Proteins / physiology*
IF 2.896
Times Cited 0
Resource
Drosophila