Article ; Online: Lysines K117 and K147 play conserved roles in Ras activation from Drosophila to mammals.
2023 Volume 13, Issue 11
Abstract: Ras signaling plays an important role in growth, proliferation, and developmental patterning. Maintaining appropriate levels of Ras signaling is important to establish patterning in development and to prevent diseases such as cancer in mature organisms. ... ...
| Abstract | Ras signaling plays an important role in growth, proliferation, and developmental patterning. Maintaining appropriate levels of Ras signaling is important to establish patterning in development and to prevent diseases such as cancer in mature organisms. The Ras protein is represented by Ras85D in Drosophila and by HRas, NRas, and KRas in mammals. In the past dozen years, multiple reports have characterized both inhibitory and activating ubiquitination events regulating Ras proteins. Inhibitory Ras ubiquitination mediated by Rabex-5 or Lztr1 is highly conserved between flies and mammals. Activating ubiquitination events at K117 and K147 have been reported in mammalian HRas, NRas, and KRas, but it is unclear if these activating roles of K117 and K147 are conserved in flies. Addressing a potential conserved role for these lysines in Drosophila Ras activation requires phenotypes strong enough to assess suppression. Therefore, we utilized oncogenic Ras, RasG12V, which biases Ras to the GTP-loaded active conformation. We created double mutants RasG12V,K117R and RasG12V,K147R and triple mutant RasG12V,K117R,K147R to prevent lysine-specific post-translational modification of K117, K147, or both, respectively. We compared their phenotypes to RasG12V in the wing to reveal the roles of these lysines. Although RasG12V,K147R did not show compelling or quantifiable differences from RasG12V, RasG12V,K117R showed visible and quantifiable suppression compared to RasG12V, and triple mutant RasG12V,K117R,K147R showed dramatic suppression compared to RasG12V and increased suppression compared to RasG12V,K117R. These data are consistent with highly conserved roles for K117 and K147 in Ras activation from flies to mammals. |
|---|---|
| MeSH term(s) | Animals ; Proto-Oncogene Proteins p21(ras)/genetics ; Drosophila/genetics ; Drosophila/metabolism ; Lysine ; ras Proteins/genetics ; ras Proteins/metabolism ; Mammals/genetics ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Ubiquitin-Protein Ligases/metabolism |
| Chemical Substances | Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2) ; Lysine (K3Z4F929H6) ; ras Proteins (EC 3.6.5.2) ; Rabex-5 protein, Drosophila (EC 6.3.2.-) ; Drosophila Proteins ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; Ras85D protein, Drosophila (EC 3.6.5.2) |
| Language | English |
| Publishing date | 2023-09-02 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, N.I.H., Extramural |
| ZDB-ID | 2629978-1 |
| ISSN | 2160-1836 ; 2160-1836 |
| ISSN (online) | 2160-1836 |
| ISSN | 2160-1836 |
| DOI | 10.1093/g3journal/jkad201 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.