Nov 23, 2017 · Here, we show that Akt activation by a Ras homolog, R-Ras, stabilizes the microtubule cytoskeleton in endothelial cells leading to endothelial lumenogenesis.

RAS signaling through PI3K is necessary for normal lymphatic vasculature development and for RAS-induced transformation in vitro and in vivo, especially in lung cancer, where it is essential for tumor initiation and necessary for tumor maintenance.

Jan 9, 2025 · This study underscores the pivotal role of the RAS-PI3Kα interaction in PI3Kα activation and provides a blueprint for designing PI3Kα isoform-specific inhibitors to disrupt this interaction.

Evidence emerging in recent years suggests that both oncogenic Ras signaling in tumor cells and non-oncogenic Ras signaling in stromal cells play an essential role in cancer. PI3K is one of the main Ras effectors, regulating important cellular processes such as cell viability or resistance to therapy or angiogenesis upon oncogenic Ras activation.

Feb 7, 2020 · In adenocarcinomas, CaM and KRas4B play critical roles, promoting PI3Kα/Akt signaling, particularly in pancreatic, lung, and colorectal cancers. PI3Kα is a ubiquitous lipid kinase that converts PIP 2 to PIP 3.

Two distinct pathways downstream of RAS orchestrate the morphology of sensory axons in vitro – RAF signaling drives elongation while enhanced AKT signaling increases axon caliber and branching (Markus et al., 2002).

Introduction: The RAS/RAF/MAP kinase-ERK kinase (MEK)/extracellular-signal-regulated kinase (ERK) (MAPK) and the PI3K/AKT/mammalian target of rapamycin (mTOR) (PI3K) pathways are frequently deregulated in human cancer as a result of genetic alterations in their components or upstream activation of cell-surface receptors.

Feb 15, 2016 · This review focuses primarily on the Ras/Raf/MEK/ERK and PI3K/Akt/mTOR signaling pathways as therapeutic targets of anticancer drugs, their specific and dual inhibitors, structure activity relationships (SARs) and inhibitors under clinical trials.

Ras recruitment can shift the PI3Kα ensemble toward a population where the kinase domain surface and the active site position and orientation favor PIP 2 insertion. This work helps elucidate Ras-mediated PI3K activation and explores the structural basis for Ras–PI3Kα drug discovery.

Mar 26, 2024 · We found that activation of Akt, most significantly Akt3 activation, by R-Ras is important for the upregulation of Jagged1, resulting in Notch target gene induction necessary for the quiescence and junctional integrity of neighboring ECs.