Targeting small GTPases: emerging grasps on previously untamable targets, pioneered by KRAS
G Yin, J Huang, J Petela, H Jiang, Y Zhang… - Signal transduction and …, 2023 - nature.com
Abstract Small GTPases including Ras, Rho, Rab, Arf, and Ran are omnipresent molecular
switches in regulating key cellular functions. Their dysregulation is a therapeutic target for …
switches in regulating key cellular functions. Their dysregulation is a therapeutic target for …
The role of KRAS splice variants in cancer biology
The three mammalian RAS genes (HRAS, NRAS and KRAS) encode four proteins that play
central roles in cancer biology. Among them, KRAS is mutated more frequently in human …
central roles in cancer biology. Among them, KRAS is mutated more frequently in human …
Machine learning–driven multiscale modeling reveals lipid-dependent dynamics of RAS signaling proteins
RAS is a signaling protein associated with the cell membrane that is mutated in up to 30% of
human cancers. RAS signaling has been proposed to be regulated by dynamic …
human cancers. RAS signaling has been proposed to be regulated by dynamic …
Direct modulators of K-Ras–membrane interactions
Protein–membrane interactions (PMIs) are ubiquitous in cellular signaling. Initial steps of
signal transduction cascades often rely on transient and dynamic interactions with the inner …
signal transduction cascades often rely on transient and dynamic interactions with the inner …
Markov state models and molecular dynamics simulations reveal the conformational transition of the intrinsically disordered hypervariable region of K-Ras4B to the …
K-Ras4B, the most frequently mutated Ras isoform in human tumors, plays a vital part in cell
growth, differentiation, and survival. Its tail, the C-terminal hypervariable region (HVR), is …
growth, differentiation, and survival. Its tail, the C-terminal hypervariable region (HVR), is …
Recent updates on the significance of KRAS mutations in colorectal cancer biology
The most commonly mutated isoform of RAS among all cancer subtypes is KRAS. In this
review, we focus on the special role of KRAS mutations in colorectal cancer (CRC), aiming …
review, we focus on the special role of KRAS mutations in colorectal cancer (CRC), aiming …
Crystal structure reveals the full Ras: Raf interface and advances mechanistic understanding of Raf activation
The interaction between Ras and Raf-kinase through the Ras-binding (RBD) and cysteine-
rich domains (CRD) of Raf is essential for signaling through the mitogen-activated protein …
rich domains (CRD) of Raf is essential for signaling through the mitogen-activated protein …
Uncovering a membrane-distal conformation of KRAS available to recruit RAF to the plasma membrane
QN Van, CA López, M Tonelli… - Proceedings of the …, 2020 - National Acad Sciences
The small GTPase KRAS is localized at the plasma membrane where it functions as a
molecular switch, coupling extracellular growth factor stimulation to intracellular signaling …
molecular switch, coupling extracellular growth factor stimulation to intracellular signaling …
Tyrosine kinases compete for growth hormone receptor binding and regulate receptor mobility and degradation
Growth hormone (GH) acts via JAK2 and LYN to regulate growth, metabolism, and neural
function. However, the relationship between these tyrosine kinases remains enigmatic …
function. However, the relationship between these tyrosine kinases remains enigmatic …
RAS nanoclusters: dynamic signaling platforms amenable to therapeutic intervention
RAS proteins are mutated in approximately 20% of all cancers and are generally associated
with poor clinical outcomes. RAS proteins are localized to the plasma membrane and …
with poor clinical outcomes. RAS proteins are localized to the plasma membrane and …