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MAP2K1

GeneName

MAP2K1

Summary

MAP2K1, also known as MEK1 or MEK-1, is a 43kDa serine/threonine protein kinase that plays a pivotal role in the MAPK signalling pathway. It is primarily localised in the cytoplasm and nucleus, but is also found in various cellular compartments such as the axon, dendrites, and focal adhesions. MAP2K1 functions as a dual-specificity kinase, activating ERK1 and ERK2 by phosphorylating them, which in turn regulates numerous cellular processes including cell motility, differentiation, and proliferation. It is implicated in several biological processes such as central nervous system neuron differentiation, chemotaxis, and regulation of gene expression, making it essential for various developmental and physiological functions.

Importance

MAP2K1 is relevant to: - Cancer research due to its role in the MAPK pathway, which is often dysregulated in tumours - Neurological studies as it is involved in neuron differentiation and response to axon injury - Developmental biology through its contributions to heart and cerebellar cortex formation - Endocrine research, given its involvement in insulin-like growth factor receptor signalling and pancreatic cell proliferation - Understanding cellular responses to stress and injury, which can inform therapeutic strategies for neurodegenerative diseases and tissue regeneration

Top Products

For researchers investigating MAP2K1, we highly recommend the top-selling recombinant antibody, Anti-MEK1 antibody [E342] (ab32091). This antibody has been validated in knockout models, ensuring reliable performance in various applications, including Western blotting (WB), immunohistochemistry (IHC), immunocytochemistry (ICC), and flow cytometry (FC). With 60 citations, it is well-regarded in the research community, making it an excellent choice for those seeking dependable detection of MAP2K1.

Abcam Product Citation Summary

The data indicates that MAP2K1 is being investigated in various contexts, particularly in relation to cancer biology and cellular signalling pathways. The studies primarily utilise Western blotting to assess MAP2K1 expression in human lung adenocarcinoma cells and other human cell lines, as well as in mouse skin tissue. This suggests a focus on understanding the role of MAP2K1 in processes such as epithelial-mesenchymal transition (EMT), migration, invasion, and the Ras-ERK signalling pathway.

Abcam Product Citation Table

ab178876
Human
WB
Lung adenocarcinoma cells
32393740
ab178876
Human
WB
A549 and SM-MES-1 cells
31443651
ab32091
Mouse
WB
Skin tissue after DMBA treatment
28855649
ab32576
Human
WB
Human samples
34162761
ab32576
Human
WB
Human samples
30876463

Domain

The proline-rich region localized between residues 270 and 307 is important for binding to RAF1 and activation of MAP2K1/MEK1.

Function

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.

Involvement in disease

Cardiofaciocutaneous syndrome 3

CFC3

A form of cardiofaciocutaneous syndrome, a multiple congenital anomaly disorder characterized by a distinctive facial appearance, heart defects and intellectual disability. 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.

None

The disease is caused by variants affecting the gene represented in this entry.

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.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

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.

Sequence Similarities

Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.

Tissue Specificity

Widely expressed, with extremely low levels in brain.

Cellular localization

Alternative names

MEK1, PRKMK1, MAP2K1, Dual specificity mitogen-activated protein kinase kinase 1, MAP kinase kinase 1, MAPKK 1, MKK1, ERK activator kinase 1, MAPK/ERK kinase 1, MEK 1

swissprot:Q02750 entrezGene:5605 omim:176872 omim:601263 swissprot:P36507 entrezGene:5604