RasMAPK

RASMAPK refers to the Ras–mitogen-activated protein kinase signaling pathway, a highly conserved cascade that transmits signals from cell surface receptors to the nucleus to regulate proliferation, differentiation, and survival. It is often described as the RAS–RAF–MEK–ERK pathway, a core module of the broader MAP kinase signaling networks.

The core components are the RAS family of small GTPases (HRAS, KRAS, NRAS), the RAF kinase family (ARAF, BRAF, RAF1/CRAF), the MAP kinase kinases MEK1/2, and the MAP kinases ERK1/2. Activation begins when extracellular cues engage receptor tyrosine kinases, recruiting adaptor proteins (such as GRB2) and guanine nucleotide exchange factors (notably SOS) to promote GTP loading on RAS. Active GTP-bound RAS then activates RAF kinases at the plasma membrane, which in turn phosphorylate and activate MEK1/2. MEK1/2 phosphorylates ERK1/2, and activated ERK translocates to the nucleus to phosphorylate transcription factors (for example ELK1), leading to altered gene expression.

Functionally, the pathway controls cell cycle progression, differentiation, metabolism, and survival. Its proper regulation is essential for development and tissue homeostasis, while dysregulation can drive oncogenesis and other diseases. Negative feedback and regulatory layers include phosphatases and scaffold proteins (such as DUSPs and SPREDs) that temper signaling, as well as cross-talk with other pathways like PI3K–AKT.

Therapeutically, the RASMAPK pathway is a major cancer target. Inhibitors targeting BRAF (e.g., vemurafenib, dabrafenib), MEK (e.g., trametinib, cobimetinib), and, in some contexts, KRAS G12C (e.g., sotorasib, adagrasib) are used to treat tumors driven by pathway alterations, often in combination strategies to overcome resistance.