ERKMAPK

ERKMAPK refers to the extracellular signal-regulated kinase portion of the mitogen-activated protein kinase (MAPK) signaling cascade. The core ERK family consists mainly of two serine/threonine kinases, ERK1 (MAPK3) and ERK2 (MAPK1), which are highly conserved and function as key regulators of cellular responses to growth signals.

Activation and signaling flow through the pathway typically begins at receptor tyrosine kinases that activate the small GTPase Ras. Ras then activates the serine/threonine kinase Raf (MAPKKK), which phosphorylates and activates the dual-specificity kinase MEK1/2 (MAPKK). MEK1/2 subsequently phosphorylates ERK1/2 on both the threonine and tyrosine residues within the TEY activation motif, fully activating ERK. Activated ERK translocates to the cytoplasm and nucleus, where it phosphorylates a broad set of substrates, including transcription factors such as ELK1 and c-Fos, as well as cytoskeletal and metabolic regulators. This broad activity translates signals into changes in gene expression, cell cycle progression, differentiation, and survival.

Clinical and research relevance is substantial. Dysregulated ERK signaling is linked to many cancers and other diseases, due to constitutive pathway activation from mutations in Ras, Raf, or MEK. Therapeutic strategies include MEK inhibitors (e.g., trametinib, selumetinib) and ERK inhibitors, used alone or in combination therapies to counteract resistance mechanisms.

ERK activity is commonly assessed by measuring phosphorylated ERK (p-ERK) levels, reflecting pathway activation. Distinct from other MAPKs like p38 and JNK, ERK signaling is frequently associated with mitogenic and pro-survival outcomes.