Extracellular signal-regulated kinases

In

The term, "extracellular signal-regulated kinases", is sometimes used as a synonym for mitogen-activated protein kinase (MAPK), but has more recently been adopted for a specific subset of the mammalian MAPK family.^{[citation needed]}

In the

Disruption of the ERK pathway is common in cancers, especially Ras, c-Raf, and receptors such as HER2.

Mitogen-activated protein kinase 1

The molecular events linking cell surface receptors to activation of ERKs are complex. It was found that Ras GTP-binding proteins are involved in the activation of ERKs.[3] Another protein kinase, Raf-1, was shown to phosphorylate a "MAP kinase-kinase", thus qualifying as a "MAP kinase kinase kinase".^[4] The MAP kinase-kinase, which activates ERK, was named "MAPK/ERK kinase" (MEK).^[5]

Receptor-linked

Transgenic gene knockout mice lacking MAPK1 have major defects in early development.^[7] Conditional deletion of Mapk1 in B cells showed a role for MAPK1 in T-cell-dependent antibody production.^[8] A dominant gain-of-function mutant of Mapk1 in transgenic mice showed a role for MAPK1 in T-cell development.^[9] Conditional inactivation of Mapk1 in neural progenitor cells of the developing cortex lead to a reduction of cortical thickness and reduced proliferation in neural progenitor cells.^[10]

Mitogen-activated protein kinase 3

Mitogen-activated protein kinase 3 (MAPK3) is also known as extracellular signal-regulated kinase 1 (ERK1). Transgenic gene knockout mice lacking MAPK3 are viable and it is thought that MAPK1 can fulfill some MAPK3 functions in most cells.^[11] The main exception is in T cells. Mice lacking MAPK3 have reduced T cell development past the CD4+ and CD8+ stage.

Clinical significance

Activation of the ERK1/2 pathway by aberrant RAS/RAF signalling, DNA damage, and