Compartmentalized signalling: Ras proteins and signalling nanoclusters

Abstract

Differential subcellular compartmentalization of the three main Ras isoforms (H‐Ras, N‐Ras and K‐Ras) is believed to underlie their biological differences. Modulatable interactions between cellular membranes and Ras C‐terminal hypervariable region motifs determine differences in trafficking and the relative proportions of each isoform in cell‐surface signalling nanoclusters and intracellular endoplasmic reticulum/Golgi, endosomal and mitochondrial compartments. Ras regulators, effectors and scaffolds are also differentially distributed, potentially enabling preferential coupling to specific signalling pathways in each subcellular location. Here we summarize the mechanisms underlying compartment‐specific Ras signalling and the outputs generated.

Differences in the Regulation of K-Ras and H-Ras Isoforms by Monoubiquitination

“…Although the structure and sequence of the three Ras isoforms are highly conserved, they play distinct roles in signaling and cell regulation in vivo. Differences in Ras localization and activity are driven by differences in post-translational modifications (12)(13)(14)(15)(16)(17)(18)(19). Our analysis has revealed two distinct mechanisms of Ras activation through the same post-translational modification.…”

“…H-Ras and N-Ras are localized at both the plasma membrane and the Golgi, whereas K-Ras is predominately at the plasma membrane (11). Differences in Ras localization and activity are driven by differences in post-translational modifications (12)(13)(14)(15)(16)(17)(18)(19). For example, differential lipidation of the Ras isoforms within their variable C-terminal domain is essential for proper membrane targeting and localization, which is in turn necessary for proper signaling (15, 20 -24).…”

Misexpression of miR482, miR1512, and miR1515 Increases Soybean Nodulation

“…ENOD40-induced expression may perturb either one of these expressions. Interestingly, Copine-like protein was implicated in cell signaling and membrane trafficking (Damer et al, 2005;Omerovic and Prior, 2009). Unfortunately, since the only tissue overexpressing miRNAs are developing nodules, northern-blot analysis and qRT-PCR on whole roots will not be suitable for transgene or target gene expression analysis in ENOD40-induced miR1512 lines.…”

Desmoglein-1/Erbin interaction suppresses ERK activation to support epidermal differentiation

“…However, analysis of inhibitors directed at EGFR targets known to influence differentiation, like ERK, PI3K, PKC, and p38MAPK, found that only ERK inhibitors rescue differentiation in DSG1-deficient cultures (8-10, 69, 70). The question as to what dictates the preference for one branch of downstream EGFR signaling over another continues to evoke numerous hypotheses, which highlight the diverse regulatory mechanisms guiding Ras activity (71)(72)(73)(74). Alternative Ras signaling outputs often hinge upon the availability and nature of Ras scaffolding proteins at given locations.…”