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
Found in a complex with at least BRAF, HRAS, MAP2K1, MAPK3/ERK1 and RGS14 (By similarity). Forms a heterodimer with MAP2K2/MEK2 (By similarity). Forms heterodimers with KSR2 which further dimerize to form tetramers (By similarity).
Interacts with KSR1 or KSR2 and BRAF; the interaction with KSR1 or KSR2 mediates KSR1-BRAF or KSR2-BRAF dimerization (PubMed:10409742, PubMed:29433126). Interacts with ARBB2, LAMTOR3 and RAF1 (By similarity). Interacts with MAPK1/ERK2 (PubMed:32721402).
Interacts with MORG1 (By similarity). Interacts with PPARG (PubMed:17101779). Interacts with isoform 1 of VRK2 (PubMed:20679487).
Interacts with SGK1 (PubMed:19447520). Interacts with BIRC6/bruce (PubMed:18329369). Interacts with KAT7; the interaction promotes KAT7 phosphorylation (By similarity).
Interacts with RAF1 and NEK10; the interaction is required for ERK1/2-signaling pathway activation in response to UV irradiation (PubMed:20956560). Interacts with TRAF3IP3 (PubMed:26195727). Interacts with MOS (PubMed:34779126, PubMed:35670744)
(Microbial infection) Interacts with Yersinia YopJ
Widely expressed, with extremely low levels in brain
The proline-rich region localized between residues 270 and 307 is important for binding to RAF1 and activation of MAP2K1/MEK1
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.
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.
| Cancer Type | Mutation Percentage |
|---|---|
| Central Nervous System Astrocytoma Grade Iv | 0.09% |
| Lung Adenocarcinoma | 1.22% |
| Lung Squamous Cell Carcinoma | 0.54% |
| Oesophagus Squamous Cell Carcinoma | 0.47% |
| Pancreas Ductal Carcinoma | 0.41% |
Genes with an experimentally identified or computationally predicted synthetic-lethal relationship to MAP2K1, aggregated across our SSL data sources. Click any partner node to view that gene’s page.
Nodes and edges are coloured by the SSL data source. Partners appearing in more than one source are shown in grey.
Total Trials Found: 4
| NCT ID | Condition | Brief Title | Phase | Status |
|---|---|---|---|---|
| NCT05585320 | Advanced Solid Tumor, Pancreatic Adenocarcinoma, Malignant Melanoma (Cutaneous), Non-small Cell Lung Cancer (NSCLC) | A Phase 1/2a Study of IMM-1-104 in Participants With Advanced or Metastatic Solid Tumors | PHASE1, PHASE2 | ACTIVE_NOT_RECRUITING |
| NCT05983159 | Slow-Flow Vascular Malformation, Fast-Flow Vascular Malformation, Vascular Malformations, Venous Malformation, Lymphatic Malformation, Low Flow, Lymphatic Malformation, Lymphangioma, Arteriovenous Malformations, Venous Malformation, Low Flow, Cystic Hygroma, Vascular Anomaly, Vascular Anomalies, PI3K Gene Mutation, MAP2K1 Gene Mutation, PIK3CA-related Overgrowth Spectrum, Arteriovenous Malformation (AVM), KRAS G12C, KRAS G12D | A Trial of Targeted Therapies for Patients With Slow-Flow or Fast-Flow Vascular Malformations | PHASE2 | RECRUITING |
| NCT04488003 | Advanced Solid Tumor, BRAF Gene Mutation, BRAF Gene Alteration, MEK Mutation, MEK Alteration, MAP2K1 Gene Mutation, MAP2K1 Gene Alteration, MAP2K2 Gene Mutation, MAP2K2 Gene Alteration | Study of Ulixertinib for Patients With Advanced Malignancies Harboring MEK or Atypical BRAF Alterations | PHASE2 | TERMINATED |
| NCT02881242 | Hormone-Resistant Prostate Cancer, Metastatic Prostate Carcinoma, Recurrent Prostate Carcinoma, Stage IV Prostate Cancer | Trametinib in Treating Patients With Progressive Metastatic Hormone-Resistant Prostate Cancer | PHASE2 | ACTIVE_NOT_RECRUITING |
| NCT06961565 | NF1 Mutation, Neurofibroma Plexiform, Neurofibroma, Plexiform, Neurofibromatosis Type 1 (NF1)-Related Plexiform Neurofibromas (PNs), Neurofibromatosis Type 1 (NF1) | PAS-004 in Adults Who Have Neurofibromatosis Type 1 With Plexiform Neurofibromas | PHASE1 | RECRUITING |
| NCT04534283 | Cancer, Cancer Metastatic, BRAF V600E, MEK1 Gene Mutation, MEK2 Gene Mutation, ERK Mutation, RAF1 Gene Mutation | A Basket Trial of an ERK1/2 Inhibitor (LY3214996) in Combination With Abemaciclib. | PHASE2 | TERMINATED |
| NCT03434262 | Anaplastic Astrocytoma, Anaplastic Ependymoma, Anaplastic Ganglioglioma, Anaplastic Meningioma, Anaplastic Oligodendroglioma, Pleomorphic Xanthoastrocytoma, Anaplastic, Atypical Teratoid/Rhabdoid Tumor, Brain Cancer, Brain Tumor, Central Nervous System Neoplasms, Choroid Plexus Carcinoma, CNS Embryonal Tumor With Rhabdoid Features, Ganglioneuroblastoma of Central Nervous System, CNS Tumor, Embryonal Tumor of CNS, Ependymoma, Glioblastoma, Glioma, Glioma, Malignant, Medulloblastoma, Medulloblastoma; Unspecified Site, Medulloepithelioma, Neuroepithelial Tumor, Neoplasms, Neoplasms, Neuroepithelial, Papillary Tumor of the Pineal Region (High-grade Only), Pediatric Brain Tumor, Pineal Parenchymal Tumor of Intermediate Differentiation (High-grade Only), Pineoblastoma, Primitive Neuroectodermal Tumor, Recurrent Medulloblastoma, Refractory Brain Tumor, Neuroblastoma. CNS, Glioblastoma, IDH-mutant, Glioblastoma, IDH-wildtype, Medulloblastoma, Group 3, Medulloblastoma, Group 4, Glioma, High Grade, Neuroepithelial Tumor, High Grade, Medulloblastoma, SHH-activated and TP53 Mutant, Medulloblastoma, SHH-activated and TP53 Wildtype, Medulloblastoma, Chromosome 9q Loss, Medulloblastoma, Non-WNT Non-SHH, NOS, Medulloblastoma, Non-WNT/Non-SHH, Medulloblastoma, PTCH1 Mutation, Medulloblastoma, WNT-activated, Ependymoma, Recurrent, Glioma, Recurrent High Grade, Glioma, Recurrent Malignant, Embryonal Tumor, NOS, Glioma, Diffuse Midline, H3K27M-mutant, Embryonal Tumor With Multilayered Rosettes (ETMR), Ependymoma, NOS, WHO Grade III, Ependymoma, NOS, WHO Grade II, Medulloblastoma, G3/G4, Ependymoma, RELA Fusion Positive | SJDAWN: St. Jude Children's Research Hospital Phase 1 Study Evaluating Molecularly-Driven Doublet Therapies for Children and Young Adults With Recurrent Brain Tumors | PHASE1 | COMPLETED |
| NCT06098872 | Arteriovenous Malformations | Pilot Study on Trametinib for Surgical Unruptured AVMs | PHASE2 | UNKNOWN |
| NCT03566485 | Stage III Breast Cancer, Stage IIIA Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer, Stage IV Breast Cancer, Estrogen Receptor-positive, HER2/Neu Negative | Atezolizumab and Cobimetinib or Idasanutlin in Participants With Stage IV or Unresectable Recurrent Estrogen Receptor Positive Breast Cancer | PHASE1, PHASE2 | TERMINATED |
| NCT03087071 | EGFR NP_005219.2:p.S492R, KRAS Gene Mutation, MAP2K1 Gene Mutation, Metastatic Colorectal Adenocarcinoma, Refractory Colorectal Adenocarcinoma, Stage IV Colorectal Cancer AJCC v7, Stage IVA Colorectal Cancer AJCC v7, Stage IVB Colorectal Cancer AJCC v7 | Panitumumab With or Without Trametinib in Treating Patients With Stage IV Colorectal Cancer | PHASE2 | ACTIVE_NOT_RECRUITING |