RasGTP

RasGTP refers to the GTP-bound, active state of Ras, a small GTPase in the Ras superfamily. In cells, Ras cycles between an inactive GDP-bound form and an active GTP-bound form. Activation is promoted by guanine nucleotide exchange factors (GEFs), which catalyze the exchange of GDP for GTP and shift Ras into RasGTP. In this state, Ras interacts with downstream effector proteins such as RAF kinases (triggering the MAPK/ERK signaling pathway), phosphoinositide 3-kinase (PI3K-AKT pathway), and RalGDS family members, leading to changes in gene expression, cell cycle progression, survival, and cytoskeletal organization.

Termination of signaling is accomplished by intrinsic GTP hydrolysis, accelerated by GTPase-activating proteins (GAPs). Ras must be localized to the inner face of the plasma membrane to signal effectively; this localization is achieved through post-translational lipid modifications at its C-terminus, including farnesylation and often palmitoylation.

Mutations in Ras genes that reduce GTPase activity or impair GAP regulation bias Ras toward the RasGTP state, creating constitutive signaling associated with oncogenesis. The most common oncogenic Ras isoforms are KRAS, HRAS, and NRAS, frequently mutated at codons 12, 13, or 61.

In research and diagnostics, RasGTP levels are commonly assessed by pull-down assays using effector domains such as RAF1-RBD or RalGDS-RBD that selectively bind GTP-bound Ras, or by fluorescence-based biosensors that report on RasGTP in living cells. RasGTP represents the active signaling configuration of Ras that dictates downstream cellular responses.