The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
Human MAP2K2 encodes mitogen-activated protein kinase kinase 2 (MEK2), an approximately 45-kDa dual-specificity protein kinase and the protein represented by the supplied UniProt accession P36507. Its primary role is highly specific: activated MEK2 transfers phosphate from ATP to both the threonine and tyrosine residues in the activation-loop TEY motif of ERK1/MAPK3 and ERK2/MAPK1, thereby activating the terminal kinases of the canonical RAS–RAF–MEK–ERK cascade. MEK2 is activated principally through phosphorylation of its own activation loop at Ser222 and Ser226. It functions mainly in cytoplasmic, membrane-associated, and scaffold-organized signaling complexes, while also controlling ERK nucleocytoplasmic trafficking. (martinvega2023navigatingtheerk12 pages 4-5)
MAP2K2 is not simply interchangeable with MAP2K1/MEK1. Their kinase domains are about 90% conserved, but MEK2 lacks the MEK1-specific ERK feedback-phosphorylation site Thr292, a difference that may permit more sustained ERK signaling under some conditions. Pathogenic germline activation causes cardiofaciocutaneous syndrome type 4 (CFC4), whereas uncommon somatic activating variants occur in cancer and can confer allele-dependent responses to MEK inhibitors. Most available drugs inhibit both MEK1 and MEK2; no established clinical application currently depends on selective MEK2 inhibition. (martinvega2023navigatingtheerk12 pages 4-5, hanrahan2020leveragingsystematicfunctional pages 10-12, hanrahan2020leveragingsystematicfunctional pages 12-15)
The literature consistently uses MAP2K2 and MEK2 synonymously and identifies the product as the second ERK-specific MAPK kinase downstream of RAF. This matches the supplied UniProt description—“dual specificity mitogen-activated protein kinase kinase 2,” also called MAPKK2, ERK activator kinase 2, or MEK2—and is distinct from its paralog MAP2K1/MEK1. The reviewed literature describes MEK2 as approximately 45 kDa. (martinvega2023navigatingtheerk12 pages 4-5, koslaUnknownyearmap2k2(mek2)in pages 1-4)
The accession-level mapping to P36507 comes from the UniProt record specified in the question; the retrieved articles generally identify the protein by MAP2K2/MEK2 rather than by UniProt accession. Nothing retrieved conflicts with that mapping.
This report concerns Homo sapiens MAP2K2. Human tumor cohorts, human RASopathy genetics, and human-cell experiments all use MAP2K2 to denote MEK2. Literature concerning MAP2K1/MEK1 or Map2k2 in nonhuman organisms was not substituted for the target; broader MEK1/2 evidence is explicitly labeled as class-level evidence.
The supplied annotations—STE-family protein kinase, protein-kinase ATP-binding site, catalytic Ser/Thr-kinase signature, and MAP kinase kinase domain—are coherent with the literature. MEK2 has the bilobal catalytic kinase architecture, an activation segment containing Ser222/Ser226, regulatory N-terminal elements, an ERK-selective docking region, and an N-terminal nuclear-export sequence. Comparative analysis found approximately 80% nucleotide identity between MAP2K1 and MAP2K2 and 90% conservation across their kinase domains; their negative-regulatory and helix-C regions differ at only one aligned residue. (martinvega2023navigatingtheerk12 pages 4-5, hanrahan2020leveragingsystematicfunctional pages 10-12)
The functional reaction can be summarized as:
ATP + ERK1/ERK2 → ADP + phospho-ERK1/ERK2
MEK2 is termed dual-specificity because it phosphorylates both a tyrosine and a threonine within the conserved ERK activation-loop TEY sequence. The current mechanistic model is sequential phosphorylation—tyrosine followed by threonine—and complete dual phosphorylation produces an approximately 50,000-fold increase in ERK activity. (martinvega2023navigatingtheerk12 pages 4-5)
The best-established direct physiological substrates are ERK1/MAPK3 and ERK2/MAPK1. This narrow specificity distinguishes MEK2 from many Ser/Thr kinases with broad substrate repertoires. An ERK-binding region near the MEK N-terminus helps recognize and retain ERK, supporting both catalytic fidelity and spatial control. (martinvega2023navigatingtheerk12 pages 4-5, koslaUnknownyearmap2k2(mek2)in pages 1-4)
Claims that MEK2 directly phosphorylates the many downstream proteins controlled by ERK should therefore be avoided: MEK2 activates ERK1/2, and activated ERK then phosphorylates numerous cytoplasmic and nuclear effectors.
In the canonical pathway, extracellular growth factors or mitogens activate receptor-proximal signaling, RAS-GTP, and RAF-family MAP3Ks. RAF then activates MEK2 by phosphorylating Ser222 and Ser226 in its activation loop. Active MEK2 phosphorylates ERK1/2, creating the core kinase relay:
RTK/RAS → RAF → MEK2 → ERK1/2 → cytoplasmic and nuclear effectors. (martinvega2023navigatingtheerk12 pages 4-5)
MEK1/2 also integrate noncanonical upstream inputs. Reviews identify MOS, MEKK1, TPL2/COT, MAST1, mixed-lineage kinases, PLK1, and other kinases as possible regulators in particular cellular or treatment contexts. These interactions are substantially less universal than RAF-dependent activation and are often supported at the MEK1/2-class rather than uniquely MEK2 level. (yang2019comprehensiveanalysisof pages 2-3, martinvega2023navigatingtheerk12 pages 4-5)
Inactive MEK proteins are constrained by N-terminal negative-regulatory and helix-C-associated structural elements. Activating substitutions or in-frame deletions in these regions can destabilize the inactive conformation, increase basal kinase activity, or reduce RAF dependence. Cancer-associated MEK alterations are consequently divided into RAF-independent, RAF-regulated, and RAF-dependent functional classes. (martinvega2023navigatingtheerk12 pages 4-5, hanrahan2020leveragingsystematicfunctional pages 12-15)
Functional testing supports this model for MEK2. In a cohort of 42,434 matched tumors and normal samples, all 14 MEK2 variants selected because they corresponded to activating MEK1 substitutions increased ERK phosphorylation; none of 12 variants corresponding to experimentally benign MEK1 variants did so. Activating positions included F57, Q60, V64, C125, P128, and Y134, while the germline in-frame deletion L46_E55del was also activating. (hanrahan2020leveragingsystematicfunctional pages 10-12)
MEK1 and MEK2 have overlapping biochemical functions and can compensate for one another in some systems, but complete equivalence is not supported. In addition to expression-dose and tissue-context effects, an important sequence distinction is that MEK1 can be feedback-phosphorylated by ERK at Thr292, facilitating dephosphorylation of its activation loop. MEK2 lacks the equivalent feedback site and may therefore support more sustained ERK activation when MEK1 is absent or downregulated. (martinvega2023navigatingtheerk12 pages 4-5, hanrahan2020leveragingsystematicfunctional pages 17-19)
This distinction is an authoritative interpretation rather than evidence that MEK2 always generates longer signals. Signal duration also depends on upstream input, phosphatases, protein abundance, scaffold composition, and cellular compartment.
MEK2 is principally an intracellular, predominantly cytosolic signaling enzyme, not a secreted protein or transmembrane receptor. Its nuclear-export sequence favors cytoplasmic localization. MEK binds inactive ERK in the cytoplasm and can promote ERK export from the nucleus through XPO1/CRM1, thus acting both as an enzyme and as an ERK anchor or trafficking factor. After stimulation, activated ERK dissociates and can act at the plasma membrane, endomembranes, cytoskeleton, cytosol, or nucleus. (martinvega2023navigatingtheerk12 pages 4-5)
Localization is also scaffold-dependent. KSR-family scaffolds assemble RAF, MEK1/2, and ERK components near signaling membranes and use a proline-rich MEK-binding sequence for constitutive association. Other ERK-pathway scaffolds organize signaling at endosomes and additional compartments. Such organization controls signal amplitude, duration, and substrate access rather than changing MEK2’s fundamental ERK1/2 specificity. (martinvega2023navigatingtheerk12 pages 4-5)
Care is required with scaffold assignments: some complexes discriminate between MEK1 and MEK2. Therefore, evidence that a scaffold binds “MEK” or MEK1 should not automatically be annotated as a direct MEK2 interaction.
MEK2 is the penultimate kinase in a pathway converting extracellular signals into ERK-dependent changes in transcription, protein translation, metabolism, cell-cycle progression, differentiation, survival, migration, and stress responses. These outputs are not independent catalytic functions of MEK2; they are downstream consequences of the strength, duration, and location of ERK activation. (yang2019comprehensiveanalysisof pages 1-2, martinvega2023navigatingtheerk12 pages 4-5)
This distinction explains apparent pleiotropy. The same MEK–ERK module can support proliferation in one context and differentiation, arrest, or death in another. Functional annotation should therefore prioritize the precise role—activation and spatial organization of ERK1/2—over assigning every downstream phenotype directly to MAP2K2.
Heterozygous pathogenic MAP2K2 variants cause cardiofaciocutaneous syndrome type 4, part of the RASopathy spectrum. The usual mechanism is dysregulated or gain-of-function MEK2 signaling, commonly through missense variants or small in-frame deletions, producing excessive or mistimed ERK1/2 activation during development. CFC is characterized broadly by craniofacial, cardiac, ectodermal, growth, gastrointestinal, and neurodevelopmental abnormalities. (koslaUnknownyearmap2k2(mek2)ina pages 1-4, koslaUnknownyearmap2k2(mek2)in pages 1-4)
The functional evidence is stronger than association alone: the CFC-associated L46_E55del MEK2 allele activated ERK in a cellular assay. A compiled clinical roadmap reported lower epilepsy frequency in MAP2K2-related CFC than in MAP2K1-related disease—approximately 30% versus 61%—but this estimate derives from rare-disease cohorts and should not be treated as a stable population prevalence. (koslaUnknownyearmap2k2(mek2)ina pages 1-4, hanrahan2020leveragingsystematicfunctional pages 10-12)
Current management is multidisciplinary and phenotype-directed. MEK inhibitors have been proposed as pathway-directed therapy, but routine treatment of MAP2K2-CFC with these agents is not established; developmental timing, chronic toxicity, and the possibility that different variants respond differently remain major barriers.
MAP2K2 mutations are uncommon relative to alterations in RAS or BRAF. The 2023 ERK-cascade review estimates MEK mutations collectively at less than 1% of human cancers. In the large functional-genomics cohort, MAP2K2 alterations occurred in 294 of 42,434 tumors (0.7%). (martinvega2023navigatingtheerk12 pages 4-5, hanrahan2020leveragingsystematicfunctional pages 10-12)
The low frequency creates a variant-interpretation problem: recurrence alone is often underpowered. Hanrahan and colleagues therefore combined hotspot statistics, three-dimensional structural analysis, evolutionary conservation, germline pathogenicity, and MAP2K1–MAP2K2 paralogy with experimental ERK-phosphorylation assays. This approach separated activating drivers from likely passengers but also showed that biochemical activation does not by itself predict drug sensitivity. (hanrahan2020leveragingsystematicfunctional pages 10-12, hanrahan2020leveragingsystematicfunctional pages 12-15)
Open Targets integrates genetic, somatic, literature, and other evidence linking MAP2K2 to cancer, melanoma, CFC, Noonan syndrome, and the broader RASopathy category. These scores support prioritization but are aggregated association measures, not clinical penetrance estimates or proof of causality for every listed disease. (OpenTargets Search: -MAP2K2)
Allosteric MEK inhibitors such as trametinib, cobimetinib, binimetinib, and selumetinib are generally MEK1/2 inhibitors, not selective MAP2K2 drugs. Their clearest real-world use is suppression of oncogenic RAS–RAF–MEK–ERK signaling in molecularly selected cancers. The clinical effect cannot normally be attributed specifically to MEK2 because both paralogs are inhibited. A 2019 review reported that three MEK1/2 inhibitors had already received FDA approval in BRAFV600E/K-oriented treatment settings at that time. (yang2019comprehensiveanalysisof pages 1-2)
Activating MEK2 alleles showed markedly variable sensitivity to trametinib in cell assays. By contrast, the ATP-competitive ERK1/2 inhibitor SCH772984 more uniformly suppressed downstream RSK phosphorylation across the tested MEK1/2 missense and deletion mutants. This suggests that some MEK2-driven tumors may be better controlled by targeting ERK below the mutant kinase, although that conclusion remains variant- and context-dependent rather than a general treatment rule. (hanrahan2020leveragingsystematicfunctional pages 12-15)
Resistance can arise through upstream pathway reactivation, altered MEK conformation, RAF-independent activation, compensatory kinases, or signaling-network adaptation. Helix-C or negative-regulatory-region alterations can be less responsive to allosteric inhibitors because those drugs depend on particular inactive-state conformations. Consequently, experts recommend functional assessment of the exact allele rather than treating every MAP2K2 variant as equivalent. (yang2019comprehensiveanalysisof pages 2-3, hanrahan2020leveragingsystematicfunctional pages 12-15)
A practical precision-oncology workflow is therefore: establish whether the variant activates ERK, determine its RAF dependence, test sensitivity to MEK and ERK inhibitors, and account for lineage-specific co-alterations. The evidence does not support prescribing a MEK inhibitor solely because sequencing reports a MAP2K2 variant of uncertain significance.
The most useful recent synthesis is Martín-Vega and Cobb’s October 2023 review, Navigating the ERK1/2 MAPK Cascade (DOI/URL). It emphasizes compartmentalization, scaffolds, feedback, mutation classes, and the non-equivalence of MEK1 and MEK2, including the absence of the MEK1 Thr292 feedback site in MEK2. (martinvega2023navigatingtheerk12 pages 4-5)
A January 2024 mechanistic study found a function that was experimentally selective for MEK2. In primary lung fibroblasts, siRNA depletion of MEK2—but not MEK1—reduced uptake of MDA-MB-231 breast-cancer extracellular vesicles. Wild-type MEK2 increased uptake, whereas kinase-inactive K101A MEK2 did not. Experiments used a 6-hour EV exposure and three wells per group. This supports a catalytic role for MEK2 in macropinocytic EV uptake and raises the hypothesis that MEK2 inhibition could disrupt preparation of the lung metastatic niche. It remains cell-culture evidence, not a demonstrated antimetastatic therapy in patients. Publication: Wan et al., January 2024, DOI/URL. (wan2024lungfibroblaststake pages 9-10)
A 2024 genomic study of head-and-neck squamous-cell-carcinoma brain metastases reported MAP2K2 alterations in 11.8% of brain-metastasis samples versus 6.4% of local tumors (P=0.005). The overall series contained 61 brain-metastasis cases, with 37 in the Foundation Medicine genomic comparison. This enrichment is hypothesis-generating: “MAP2K2 alteration” may include biologically heterogeneous events, and the study does not establish that MEK2 activation causes brain dissemination. Publication: Dennis et al., October 2024, DOI/URL. (OpenTargets Search: -MAP2K2)
The evidence below summarizes which findings are genuinely MEK2-specific and which derive from the broader MEK1/2 class.
| Topic | Best-supported finding | Evidence type / specificity | Key quantitative result | Source / date / URL |
|---|---|---|---|---|
| Identity and primary function | Human MAP2K2 (MEK2) is an approximately 45-kDa, ERK-specific dual-specificity MAPK kinase downstream of RAF; it activates MAPK3/ERK1 and MAPK1/ERK2. This agrees with the supplied UniProt P36507 identity. | MEK2-specific identity; MEK1/2-class pathway evidence | Approximate mass: 45 kDa | Martín-Vega & Cobb, Oct 2023, DOI (martinvega2023navigatingtheerk12 pages 4-5) |
| Activation and localization | MEK2 is activated by phosphorylation at Ser222 and Ser226. Its N-terminal ERK-binding region and nuclear-export sequence favor cytosolic MEK–ERK association and CRM1/XPO1-dependent ERK export; unlike MEK1, MEK2 lacks the MEK1-specific ERK-feedback site Thr292. | Activation sites are MEK2-specific; docking, export, and localization are predominantly MEK1/2-class evidence | Dual phosphorylation of the ERK TEY motif increases ERK activity by approximately 50,000-fold | Martín-Vega & Cobb, Oct 2023, DOI (martinvega2023navigatingtheerk12 pages 4-5) |
| Cancer-variant profiling | MAP2K2 alterations are uncommon, but functional testing showed that MEK2 variants paralogous to activating MEK1 variants induced ERK phosphorylation; variants corresponding to benign MEK1 variants did not. Trametinib response varied by allele. | MEK2-specific tumor profiling and cellular functional assays; paralogy-assisted interpretation | Alterations in 294/42,434 tumors (0.7%); 14/14 predicted activating variants activated ERK, versus 0/12 predicted benign variants | Hanrahan et al., online Jul 8, 2020; issue Oct 2020, DOI (hanrahan2020leveragingsystematicfunctional pages 10-12, hanrahan2020leveragingsystematicfunctional pages 12-15) |
| Cardiofaciocutaneous syndrome type 4 | Germline activating MAP2K2 variants cause CFC4, a RASopathy associated with persistent ERK1/2 hyperactivation; the in-frame L46_E55del variant was experimentally activating. | Human genetic association plus MEK2-specific functional assay | Reported epilepsy risk: 30% for MAP2K2-related CFC versus 61% for MAP2K1-related CFC; one roadmap reported 54 unique public MAP2K2 DNA variants | Scorrano et al., Nov 2023, DOI; Hanrahan et al., 2020, DOI (koslaUnknownyearmap2k2(mek2)ina pages 1-4, hanrahan2020leveragingsystematicfunctional pages 10-12) |
| Lung-fibroblast extracellular-vesicle uptake | In primary lung fibroblasts, MEK2 knockdown—but not MEK1 knockdown—reduced uptake of MDA-MB-231 breast-cancer extracellular vesicles. Wild-type MEK2 increased uptake, whereas kinase-inactive K101A did not, supporting a catalytic role in macropinocytosis. | MEK2-specific mechanistic cell-culture evidence; not a clinical implementation | EV exposure: 6 hours; n=3 wells per group; reported significance thresholds ranged from P<0.05 to P<0.001, but effect sizes were not supplied in the retrieved excerpt | Wan et al., Jan 2024, DOI (wan2024lungfibroblaststake pages 9-10) |
| HNSCC brain-metastasis enrichment | MAP2K2 alterations were enriched in head-and-neck squamous-cell carcinoma brain metastases relative to local tumors, identifying a hypothesis-generating association rather than proof that MAP2K2 drives metastasis. | Human tumor-genomic association; alteration-level rather than functionally validated MEK2 mechanism | 11.8% versus 6.4%; P=0.005; total cohort 61 brain-metastasis cases, including 37 in the genomic comparison | Dennis et al., Oct 2024, DOI (OpenTargets Search: -MAP2K2) |
Table: Evidence table distinguishing direct MEK2 findings from broader MEK1/2-class knowledge. It summarizes molecular function, disease genetics, variant statistics, and notable 2024 observations with study-level limitations.
High-confidence primary annotation: MAP2K2 encodes human MEK2, an ERK1/2-selective dual-specificity kinase activated at Ser222/Ser226. Its core physiological task is activation and spatial control of ERK1/2. (martinvega2023navigatingtheerk12 pages 4-5)
High-confidence localization annotation: MEK2 functions predominantly in intracellular cytoplasmic and scaffold-organized complexes and contributes to CRM1-dependent ERK nuclear export. It is neither secreted nor a membrane-spanning transporter. (martinvega2023navigatingtheerk12 pages 4-5)
Moderate-confidence paralog distinction: Absence of the MEK1 Thr292 feedback site provides a plausible mechanism for more sustained MEK2-dependent ERK activation, but cellular phenotype remains strongly context- and dosage-dependent. (martinvega2023navigatingtheerk12 pages 4-5)
Strong variant-level caution: MAP2K2 alterations are rare, and drug sensitivity is allele-specific. Paralogy and structural inference are useful because the kinase domains are highly conserved, but experimental validation remains necessary. (hanrahan2020leveragingsystematicfunctional pages 10-12, hanrahan2020leveragingsystematicfunctional pages 12-15)
Translational limitation: Existing clinical MEK inhibition is primarily class-level MEK1/2 targeting. Selective MEK2 inhibition is a research strategy rather than an established clinical implementation, and recent MEK2-specific findings—such as EV uptake by lung fibroblasts—remain preclinical. (wan2024lungfibroblaststake pages 9-10)
The defensible functional annotation for human MAP2K2/P36507 is: a predominantly cytoplasmic, ERK-specific dual-specificity MAP kinase kinase that is activated mainly by RAF-dependent phosphorylation at Ser222/Ser226 and activates ERK1 and ERK2 by dual phosphorylation of their TEY activation loops. N-terminal ERK docking, nuclear export, and scaffold recruitment couple catalysis to compartmentalized signaling. Germline activating variants cause CFC4, while rare somatic variants can act as cancer drivers or resistance alleles. Recent research strengthens the view that MEK2 has context-specific functions not always shared by MEK1, but clinical pharmacology still largely treats MEK1 and MEK2 as a combined target.
References
(martinvega2023navigatingtheerk12 pages 4-5): Ana Martín-Vega and Melanie H. Cobb. Navigating the erk1/2 mapk cascade. Biomolecules, 13(10):1555, Oct 2023. URL: https://doi.org/10.3390/biom13101555, doi:10.3390/biom13101555. This article has 137 citations.
(hanrahan2020leveragingsystematicfunctional pages 10-12): Aphrothiti J. Hanrahan, Brooke E. Sylvester, Matthew T. Chang, Arijh Elzein, Jianjiong Gao, Weiwei Han, Ye Liu, Dong Xu, Sizhi P. Gao, Alexander N. Gorelick, Alexis M. Jones, Amber J. Kiliti, Moriah H. Nissan, Clare A. Nimura, Abigail N. Poteshman, Zhan Yao, Yijun Gao, Wenhuo Hu, Hannah C. Wise, Elena I. Gavrila, Alexander N. Shoushtari, Shakuntala Tiwari, Agnes Viale, Omar Abdel-Wahab, Taha Merghoub, Michael F. Berger, Neal Rosen, Barry S. Taylor, and David B. Solit. Leveraging systematic functional analysis to benchmark an in silico framework distinguishes driver from passenger mek mutants in cancer. Oct 2020. URL: https://doi.org/10.1158/0008-5472.can-20-0865, doi:10.1158/0008-5472.can-20-0865. This article has 40 citations and is from a highest quality peer-reviewed journal.
(hanrahan2020leveragingsystematicfunctional pages 12-15): Aphrothiti J. Hanrahan, Brooke E. Sylvester, Matthew T. Chang, Arijh Elzein, Jianjiong Gao, Weiwei Han, Ye Liu, Dong Xu, Sizhi P. Gao, Alexander N. Gorelick, Alexis M. Jones, Amber J. Kiliti, Moriah H. Nissan, Clare A. Nimura, Abigail N. Poteshman, Zhan Yao, Yijun Gao, Wenhuo Hu, Hannah C. Wise, Elena I. Gavrila, Alexander N. Shoushtari, Shakuntala Tiwari, Agnes Viale, Omar Abdel-Wahab, Taha Merghoub, Michael F. Berger, Neal Rosen, Barry S. Taylor, and David B. Solit. Leveraging systematic functional analysis to benchmark an in silico framework distinguishes driver from passenger mek mutants in cancer. Oct 2020. URL: https://doi.org/10.1158/0008-5472.can-20-0865, doi:10.1158/0008-5472.can-20-0865. This article has 40 citations and is from a highest quality peer-reviewed journal.
(koslaUnknownyearmap2k2(mek2)in pages 1-4): M Kośla. Map2k2 (mek2) in cardiofaciocutaneous (cfc) syndrome-research roadmap. Unknown journal, Unknown year.
(yang2019comprehensiveanalysisof pages 2-3): Lei Yang, Liangzhen Zheng, Wee Joo Chng, and Jeak Ling Ding. Comprehensive analysis of erk1/2 substrates for potential combination immunotherapies. Trends in pharmacological sciences, 40:897-910, Nov 2019. URL: https://doi.org/10.1016/j.tips.2019.09.005, doi:10.1016/j.tips.2019.09.005. This article has 96 citations and is from a highest quality peer-reviewed journal.
(hanrahan2020leveragingsystematicfunctional pages 17-19): Aphrothiti J. Hanrahan, Brooke E. Sylvester, Matthew T. Chang, Arijh Elzein, Jianjiong Gao, Weiwei Han, Ye Liu, Dong Xu, Sizhi P. Gao, Alexander N. Gorelick, Alexis M. Jones, Amber J. Kiliti, Moriah H. Nissan, Clare A. Nimura, Abigail N. Poteshman, Zhan Yao, Yijun Gao, Wenhuo Hu, Hannah C. Wise, Elena I. Gavrila, Alexander N. Shoushtari, Shakuntala Tiwari, Agnes Viale, Omar Abdel-Wahab, Taha Merghoub, Michael F. Berger, Neal Rosen, Barry S. Taylor, and David B. Solit. Leveraging systematic functional analysis to benchmark an in silico framework distinguishes driver from passenger mek mutants in cancer. Oct 2020. URL: https://doi.org/10.1158/0008-5472.can-20-0865, doi:10.1158/0008-5472.can-20-0865. This article has 40 citations and is from a highest quality peer-reviewed journal.
(yang2019comprehensiveanalysisof pages 1-2): Lei Yang, Liangzhen Zheng, Wee Joo Chng, and Jeak Ling Ding. Comprehensive analysis of erk1/2 substrates for potential combination immunotherapies. Trends in pharmacological sciences, 40:897-910, Nov 2019. URL: https://doi.org/10.1016/j.tips.2019.09.005, doi:10.1016/j.tips.2019.09.005. This article has 96 citations and is from a highest quality peer-reviewed journal.
(koslaUnknownyearmap2k2(mek2)ina pages 1-4): M Kośla. Map2k2 (mek2) in cardiofaciocutaneous (cfc) syndrome-research roadmap. Unknown journal, Unknown year.
(OpenTargets Search: -MAP2K2): Open Targets Query (-MAP2K2, 5 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.
(wan2024lungfibroblaststake pages 9-10): Yuhao Wan, Yue Zhao, Minghui Cao, Jingyi Wang, Sheila V. Tran, Zhixuan Song, Brent W. Hsueh, and Shizhen Emily Wang. Lung fibroblasts take up breast cancer cell-derived extracellular vesicles partially through mek2-dependent macropinocytosis. Jan 2024. URL: https://doi.org/10.1158/2767-9764.crc-23-0316, doi:10.1158/2767-9764.crc-23-0316. This article has 8 citations and is from a peer-reviewed journal.