MAP2K1

The protein encoded by this gene is a member of the dual specificity protein kinase family, which acts as a mitogen-activated protein (MAP) kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. This protein kinase lies upstream of MAP kinases and stimulates the enzymatic activity of MAP kinases upon wide variety of extra- and intracellular signals. As an essential component of MAP kinase signal transduction pathway, this kinase is involved in many cellular processes such as proliferation, differentiation, transcription regulation and development. [provided by RefSeq, Jul 2008]

mitogen-activated protein kinase kinase 1

Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Binding of extracellular ligands such as growth factors, cytokines and hormones to their cell-surface receptors activates RAS and this initiates RAF1 activation. RAF1 then further activates the dual-specificity protein kinases MAP2K1/MEK1 and MAP2K2/MEK2. Both MAP2K1/MEK1 and MAP2K2/MEK2 function specifically in the MAPK/ERK cascade, and catalyze the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in the extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2, leading to their activation and further transduction of the signal within the MAPK/ERK cascade. Activates BRAF in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF dimerization and BRAF activation (PubMed:29433126).
Depending on the cellular context, this pathway mediates diverse biological functions such as cell growth, adhesion, survival and differentiation, predominantly through the regulation of transcription, metabolism and cytoskeletal rearrangements. One target of the MAPK/ERK cascade is peroxisome proliferator-activated receptor gamma (PPARG), a nuclear receptor that promotes differentiation and apoptosis. MAP2K1/MEK1 has been shown to export PPARG from the nucleus. The MAPK/ERK cascade is also involved in the regulation of endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC), as well as in the fragmentation of the Golgi apparatus during mitosis.

Bergmann glial cell differentiationIEA:Ensembl
Cell motilityIEA:Ensembl
Cellular senescenceManual Assertion Based On ExperimentIMP:BHF-UCL
Cerebellar cortex formationIEA:Ensembl
ChemotaxisManual Assertion Based On ExperimentTAS:ProtInc
Epithelial cell proliferation involved in lung morphogenesisIEA:Ensembl
ERK1 and ERK2 cascadeTAS:Reactome
Face developmentIEA:Ensembl
Heart developmentIEA:Ensembl
Keratinocyte differentiationIEA:Ensembl
Labyrinthine layer developmentIEA:Ensembl
MAPK cascadeManual Assertion Based On ExperimentIBA:GO_Central
Negative regulation of cell population proliferationManual Assertion Based On ExperimentIDA:BHF-UCL
Neuron differentiationManual Assertion Based On ExperimentIBA:GO_Central
Placenta blood vessel developmentIEA:Ensembl
Positive regulation of axonogenesisIEA:Ensembl
Positive regulation of ERK1 and ERK2 cascadeManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of gene expressionManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of production of miRNAs involved in gene silencing by miRNAManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of protein serine/threonine kinase activityManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIMP:BHF-UCL
Protein phosphorylationManual Assertion Based On ExperimentIDA:FlyBase
Regulation of axon regenerationIEA:Ensembl
Regulation of early endosome to late endosome transportManual Assertion Based On ExperimentTAS:UniProtKB
Regulation of Golgi inheritanceManual Assertion Based On ExperimentTAS:UniProtKB
Regulation of stress-activated MAPK cascadeManual Assertion Based On ExperimentTAS:UniProtKB
Signal transductionManual Assertion Based On ExperimentTAS:ProtInc
Thymus developmentIEA:Ensembl
Thyroid gland developmentIEA:Ensembl
Trachea formationIEA:Ensembl

Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
Cytoplasm, cytoskeleton, microtubule organizing center, spindle pole body
Cytoplasm
Nucleus
Membrane
Localizes at centrosomes during prometaphase, midzone during anaphase and midbody during telophase/cytokinesis (PubMed:14737111).
Membrane localization is probably regulated by its interaction with KSR1 (PubMed:10409742).

Cardiofaciocutaneous syndrome 3 (CFC3):
A form of cardiofaciocutaneous syndrome, a multiple congenital anomaly disorder characterized by a distinctive facial appearance, heart defects and mental retardation. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. Distinctive features of CFC3 include macrostomia and horizontal shape of palpebral fissures.
Melorheostosis, isolated (MEL):
A sclerosing bone disorder characterized by hyperostosis of the cortex of tubular bones, frequently involving one limb. The lesions may be accompanied by abnormalities of adjacent soft tissue, joint contractures, sclerodermatous skin lesions, muscle atrophy, or hemangioma.

Phosphorylation at Ser-218 and Ser-222 by MAP kinase kinase kinases (BRAF or MEKK1) positively regulates kinase activity (PubMed:29433126, PubMed:8131746).
Also phosphorylated at Thr-292 by MAPK1/ERK2 and at Ser-298 by PAK (PubMed:16129686).
MAPK1/ERK2 phosphorylation of Thr-292 occurs in response to cellular adhesion and leads to inhibition of Ser-298 phosphorylation by PAK (PubMed:16129686).
Autophosphorylated at Ser-218 and Ser-222, autophosphosphorylation is promoted by NEK10 following UV irradiation (PubMed:20956560).
(Microbial infection) Acetylation by Yersinia YopJ prevents phosphorylation and activation, thus blocking the MAPK signaling pathway.