Target intelligence / Profile preview

Mitogen-activated protein kinase signaling pathway (Ras-Raf-MEK-ERK pathway) (MAPK pathway (also called ERK pathway or Ras-Raf-MEK-ERK pathway))

Target
MAPK pathway (also called ERK pathway or Ras-Raf-MEK-ERK pathway)
Molecular classification
Enzyme, Small GTPase, Signal transduction pathway
01

Overview

The MAPK/ERK pathway (Ras-Raf-MEK-ERK pathway) is a central signal transduction cascade in eukaryotic cells, critical for transmitting extracellular growth signals to the nucleus via a sequence of phosphorylation events. It begins with activation of a cell surface receptor (often a receptor tyrosine kinase), leading to recruitment and activation of small GTPases such as Ras. Active Ras then stimulates a cascade of serine/threonine kinases — Raf (MAP3K) ➔ MEK1/2 (MAP2K) ➔ ERK1/2 (MAPK). Activated ERK translocates to the nucleus to regulate gene expression controlling cell proliferation, differentiation, and survival. Dysregulation of this pathway, particularly through oncogenic mutations in Ras or BRAF, is implicated in numerous cancers and developmental syndromes.

Other names
MAPK/ERK pathwayRas-Raf-MEK-ERK pathwayMAPK cascadeRas-MAPK pathway
02

Mechanism of action

Inhibit kinase activity (e.g., BRAF or MEK inhibitors prevent downstream signaling) Block mutant Ras protein function (e.g., direct KRAS G12C inhibition) Modulate pathway activation at the receptor or GTPase level

03

Biological functions

Signal transductionCell proliferationCell differentiationCell survivalApoptosisCell cycle regulationDevelopment
04

Disease associations

Cancer (very strong association; mutations common in many tumor types)Developmental disorders ("RASopathies" including Noonan syndrome, Costello syndrome)Other diseases involving abnormal cell proliferation
05

Safety considerations

Off-target effects from kinase inhibition (e.g., skin toxicity, cardiac effects)Resistance development (secondary mutations, pathway reactivation)Limited efficacy for direct Ras targeting due to druggability challenges
06

Interacting drugs

BRAF inhibitors (e.g., vemurafenib, dabrafenib)

3 more in the full profile.

07

Biomarkers

Mutations in KRAS, NRAS, HRASBRAF mutation status (V600E and others)MAPK pathway gene panel (for patient stratification)

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