Molecular basis of mitogen-activated protein kinase ERK2 activation by its upstream kinase MEK1

ABSTRACT: The RAS-RAF-MEK-ERK mitogen-activated protein kinase (MAPK) pathway relays extracellular signals into a cellular response by activation of transcription factors and other protein kinases. The pathway regulates functions such as cell proliferation and growth, with mutations in various nodes found in 30% of cancers. Here, we determined high-resolution structures[1.1] of the MAP2K MEK1 in complex with its substrate MAPK ERK2. We define the molecular details of specificity and phosphoryl transfer to the tyrosine of the ERK2 activation loop and examine the dynamics of substrate recognition using solution techniques and molecular dynamics. Binding of the substrate MAPK leads to activation of the MAP2K, explaining the mechanism of many disease-causing mutations. Our data advance the understanding of MAPK signalling and provide a starting point for drug development

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Oscar Vadas  

LAB HEAD: Oscar VADAS

PROVIDER: PXD073252 | Pride | 2026-10-20

REPOSITORIES: Pride