Relation Results

Summary

Name MEK1/2
Primary ID SIGNOR-PF25
Type protein family
Formed by MAP2K1, MAP2K2
Relations 62
Pathways Acute Myeloid Leukemia, BCR-ABL in AML, FLT3 in AML, KIT in AML, AML_TRIPLETS, B-cell activation, COVID-19 Causal Network, Colorectal Carcinoma, EGFR Signaling, ErbB receptors in cancer, FLT3-ITD signaling, Glioblastoma Multiforme, GLP-1 and GIP receptor signaling in PDAC, Hepatocellular Tumor, IL6 Signaling, Insulin Signaling, Inhibition of Apoptosis, Integrin Signaling, Luminal Breast Cancer, LIF in PDAC, Mitochondrial dynamics in T cell exhaustion, Malignant Melanoma, NPM1_new, Noonan syndrome, Non-small-cell lung cancer (NSCLC), Oxytocin signaling, Pancreatic ductal adenocarcinoma (PDA), PI3K/AKT Signaling, Rett syndrome, Rhabdomyosarcoma, RTKs in cancer, SARS-CoV MAPK PERTURBATION, Thyroid cancer, T cell activation, Toll like receptors, VEGF Signaling

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0.20.20.20.20.20.20.7490.20.7490.5670.3280.5670.80.4550.80.80.80.6210.6480.20.5440.80.780.2750.6040.80.2680.7440.5160.80.4780.5590.3060.7390.20.6620.3150.20.20.4220.80.7450.80.2MEK1/2TAL1IRS1TIAM1MAPK1MAPK3GSK3BERK1/2GbetaPAKCHEK1PAK1SL-327MAPK11N-[(2S)-2,3-dihydroxypropyl]-3-(2-fluoro-4-iodoanilino)-4-pyridinecarboxamideU0126U0126.EtOHMAP3K1ANXA3PPP2CA2-(2-amino-3-methoxyphenyl)chromen-4-oneBRAFPDPK1LAMTOR3trametinibPDCD1ARAFWDR83PD318088CDK1MAP3K8FGFR2RAF1CASP9MAPK14FGFR1CEBPAPPARGMAP3K22-(2-chloro-4-iodoanilino)-N-(cyclopropylmethoxy)-3,4-difluorobenzamideselumetinib

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▶Modifications Tables

Relations
Regulator
Mechanism
target
score ℹ
+ MEK1/2down-regulates img/direct_inhibition.png phosphorylation TAL1 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-244975 Ser122 DGRMVQLsPPALAAP Homo sapiens
pmid sentence
We found that hypoxia greatly accelerated tal1 turnover in these cells through mitogen-activated protein kinase (mapk)2-mediated phosphorylation, ubiquitination, and proteasomal degradation.
Publications: 1 Organism: Homo Sapiens
+ MEK1/2down-regulates img/direct_inhibition.png phosphorylation IRS1 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-244784 Ser307 TRRSRTEsITATSPA Homo sapiens
pmid sentence
Thus, at least three kinases mediate phosphorylation of ser307, including jnk, serine kinases in the pi 3-kinase cascade that are activated byinsulinor igf-1, and mek1-sensitive kinase cascades during tnf-alfa stimulation.
Publications: 1 Organism: Homo Sapiens
Tissue: Muscle
Pathways:Adipogenesis, Insulin Signaling, Luminal Breast Cancer
+ MEK1/2down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation TIAM1 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-276674 Ser329 DVNAGEGsEFADSGI Homo sapiens HEK-293T Cell
pmid sentence
Phosphorylation of Ser329, Ser334, and Thr340 in Tiam1 is required for its interaction with βTrCP1. The proteolysis of Tiam1 is prevented by βTrCP silencing, inhibition of CK1 and MEK, or mutation of the Tiam1 degron site.
Publications: 1 Organism: Homo Sapiens
+ MEK1/2up-regulates activity img/direct-activation.png phosphorylation MAPK1 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-244792 Thr185 HDHTGFLtEYVATRW Homo sapiens BJ Cell
pmid sentence
Mapk1 is phosphorylated by map2k1/mek1 and map2k2/mek2 on thr-185 and tyr-187 in response to external stimuli like insulin or ngf. Both phosphorylations are required for activity.
Identifier Residue Sequence Organism Cell Line
SIGNOR-244788 Tyr187 HTGFLTEyVATRWYR Homo sapiens BJ Cell
pmid sentence
Mapk1 is phosphorylated by map2k1/mek1 and map2k2/mek2 on thr-185 and tyr-187 in response to external stimuli like insulin or ngf. Both phosphorylations are required for activity.
Identifier Residue Sequence Organism Cell Line
SIGNOR-244795 Homo sapiens Adipocyte
pmid sentence
Mek1 as indicated by extensive phosphorylation of erk1 and erk2 during the initial 2 h of adipogenesis.
Identifier Residue Sequence Organism Cell Line
SIGNOR-258990 Mus musculus
pmid sentence
Raf proteins have been shown to phosphorylate and activate MAPKKs (MAP kinase kinases) called MEKs (MAPK or ERK kinases) which in turn phosphorylate and activate MAPKs (MAP kinases) called ERKs
Publications: 4 Organism: Homo Sapiens, Mus Musculus
+ MEK1/2up-regulates img/direct-activation.png phosphorylation MAPK3 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-244802 Thr202 HDHTGFLtEYVATRW Homo sapiens
pmid sentence
The mek1 proline-rich insert is required for efficient activation of the mitogen-activated protein kinases erk1 and erk2 in mammalian cells.
Identifier Residue Sequence Organism Cell Line
SIGNOR-244806 Tyr204 HTGFLTEyVATRWYR Homo sapiens
pmid sentence
The mek1 proline-rich insert is required for efficient activation of the mitogen-activated protein kinases erk1 and erk2 in mammalian cells.
Identifier Residue Sequence Organism Cell Line
SIGNOR-244798 Homo sapiens
pmid sentence
Mek1 as indicated by extensive phosphorylation of erk1 and erk2 during the initial 2 h of adipogenesis.
Publications: 3 Organism: Homo Sapiens
+ MEK1/2up-regulates activity img/direct-activation.png phosphorylation GSK3B 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-244780 Tyr216 RGEPNVSyICSRYYR Homo sapiens
pmid sentence
In vitro kinase assay was carried out using a recombinant human active mek1 and we found that gsk-3beta was phosphorylated on tyr(216) by this kinase in a dose- and time-dependent manner. Further, the pretreatment of fibroblasts with u0126 inhibited serum-induced nuclear translocation of gsk-3beta. These results suggested that mek1/2 induces tyrosine phosphorylation of gsk-3beta and this cellular event might induce nuclear translocation of gsk-3beta.
Publications: 1 Organism: Homo Sapiens
Tissue: Skin
Pathways:Adipogenesis, Acute Myeloid Leukemia, AML_TRIPLETS, FLT3-ITD signaling, Insulin Signaling, PI3K/AKT Signaling
+ ERK1/2down-regulates activity img/direct_inhibition.png phosphorylation MEK1/2 0.749
Identifier Residue Sequence Organism Cell Line
SIGNOR-244858 Homo sapiens HEK-293 Cell
pmid sentence
An ERK2-binding site at the N terminus of MEK1 was reported to mediate their stable association. We examined the importance of this binding site in the feedback phosphorylation of mek1 on thr(292) and thr(386) by erk2
Identifier Residue Sequence Organism Cell Line
SIGNOR-244862 Chlorocebus aethiops COS Cell
pmid sentence
We propose that activation of erk during adhesion creates a feedback system in which erk phosphorylates mek1 on t292, and this in turn blocks additional s298 phosphorylation in response to integrin signaling.
Publications: 2 Organism: Homo Sapiens, Chlorocebus Aethiops
Pathways:Adipogenesis, Acute Myeloid Leukemia, BCR-ABL in AML, FLT3 in AML, KIT in AML, AML_TRIPLETS, B-cell activation, COVID-19 Causal Network, Colorectal Carcinoma, EGFR Signaling, ErbB receptors in cancer, FLT3-ITD signaling, Glioblastoma Multiforme, Hepatocellular Tumor, IL6 Signaling, Insulin Signaling, Inhibition of Apoptosis, Integrin Signaling, Luminal Breast Cancer, Malignant Melanoma, NPM1_new, Noonan syndrome, Non-small-cell lung cancer (NSCLC), Oxytocin signaling, Pancreatic ductal adenocarcinoma (PDA), PI3K/AKT Signaling, Rett syndrome, Rhabdomyosarcoma, RTKs in cancer, SARS-CoV MAPK PERTURBATION, Thyroid cancer, T cell activation, Toll like receptors, VEGF Signaling
+ MEK1/2up-regulates img/direct-activation.png phosphorylation Gbeta 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-269913 Homo sapiens
pmid sentence
Mek1 as indicated by extensive phosphorylation of erk1 and erk2 during the initial 2 h of adipogenesis.
Publications: 1 Organism: Homo Sapiens
+ MEK1/2up-regulates img/direct-activation.png phosphorylation ERK1/2 0.749
Identifier Residue Sequence Organism Cell Line
SIGNOR-244776 Homo sapiens
pmid sentence
Mapk1 is phosphorylated by map2k1/mek1 and map2k2/mek2 on thr-185 and tyr-187 in response to external stimuli like insulin or ngf. Both phosphorylations are required for activity.
Publications: 1 Organism: Homo Sapiens
Pathways:Adipogenesis, Acute Myeloid Leukemia, BCR-ABL in AML, FLT3 in AML, KIT in AML, AML_TRIPLETS, B-cell activation, COVID-19 Causal Network, Colorectal Carcinoma, EGFR Signaling, ErbB receptors in cancer, FLT3-ITD signaling, Glioblastoma Multiforme, Hepatocellular Tumor, IL6 Signaling, Insulin Signaling, Inhibition of Apoptosis, Integrin Signaling, Luminal Breast Cancer, Malignant Melanoma, NPM1_new, Noonan syndrome, Non-small-cell lung cancer (NSCLC), Oxytocin signaling, Pancreatic ductal adenocarcinoma (PDA), PI3K/AKT Signaling, Rett syndrome, Rhabdomyosarcoma, RTKs in cancer, SARS-CoV MAPK PERTURBATION, Thyroid cancer, T cell activation, Toll like receptors, VEGF Signaling
+ PAKup-regulates img/direct-activation.png phosphorylation MEK1/2 0.567
Identifier Residue Sequence Organism Cell Line
SIGNOR-244920 Homo sapiens HeLa Cell
pmid sentence
Inhibition of pak kinase activity dramatically decreased phosphorylation of mek1 at ser(298) in response to either pdgf or egf.
Publications: 1 Organism: Homo Sapiens
+ CHEK1down-regulates activity img/indirect_inhibition.png MEK1/2 0.328
Identifier Residue Sequence Organism Cell Line
SIGNOR-263059 Homo sapiens
pmid sentence
Mechanistically, Ras-MEK signaling drives Chk1 expression and promotes cancer cell growth that produces genotoxic stress that requires Chk1 to mediate a response to the consequent DNA damage. Reciprocally, Chk1 engages a negative feedback loop to prevent hyperactivation of Ras-MEK signaling, thereby limiting DNA damage. Ras–MEK signaling transcriptionally activates Chk1, which appears to sustain cancer cell growth by maintaining DNA damage levels below a threshold that would otherwise drive apoptosis.
Publications: 1 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling
+ PAK1up-regulates activity img/direct-activation.png phosphorylation MEK1/2 0.567
Identifier Residue Sequence Organism Cell Line
SIGNOR-244924 Homo sapiens
pmid sentence
We find that adhesion to fibronectin induces pak1-dependent phosphorylation of mek1 on s298 and that this phosphorylation is necessary for efficient activation of mek1 and subsequent mapk activation.
Publications: 1 Organism: Homo Sapiens
Pathways:EGFR Signaling, T cell activation, Toll like receptors
+ SL-327down-regulates img/direct_inhibition.png chemical inhibition MEK1/2 0.8
Identifier Residue Sequence Organism Cell Line
SIGNOR-244955 Homo sapiens Neuron
pmid sentence
The mek1/2 inhibitors pd98059, sl327, and u0126 have been extensively used to implicate erk1/2 in neuroplasticity
Publications: 1 Organism: Homo Sapiens
Tissue: Brain
+ MAPK11down-regulates activity img/indirect_inhibition.png MEK1/2 0.455
Identifier Residue Sequence Organism Cell Line
SIGNOR-263512 Homo sapiens Skin Fibroblast
pmid sentence
Activation of p38 MAPK is required for arsenite-induced apoptosis and MEK1,2 dephosphorylation in human skin fibroblasts. Our data suggest the presence of a continuous negative feedback from p38α and p38β to MEK1,2 as simultaneous inhibition of p38α and p38β isoforms in normal quiescent cells resulted in accumulation of phosphorylated MEK1,2 (Fig. 2A) ⇓ . This negative regulation of MEK1,2 in normal cells could be considered a means to control MEK1,2-mediated proliferation and expression of transformation-related genes.
Publications: 1 Organism: Homo Sapiens
+ N-[(2S)-2,3-dihydroxypropyl]-3-(2-fluoro-4-iodoanilino)-4-pyridinecarboxamidedown-regulates img/direct_inhibition.png chemical inhibition MEK1/2 0.8
Identifier Residue Sequence Organism Cell Line
SIGNOR-244820 Homo sapiens
pmid sentence
Publications: 1 Organism: Homo Sapiens
+ U0126down-regulates img/direct_inhibition.png chemical inhibition MEK1/2 0.8
Identifier Residue Sequence Organism Cell Line
SIGNOR-244958 Homo sapiens
pmid sentence
The mek1/2 inhibitors pd98059, sl327, and u0126 have been extensively used to implicate erk1/2 in neuroplasticity. u0126 was found to functionally antagonize ap-1 transcriptional activity via noncompetitive the dual specificity kinase mek with an ic50 of 0.07 microm for mek 1 and 0.06 microm for mek 2.
Publications: 1 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling
+ U0126.EtOHdown-regulates img/direct_inhibition.png chemical inhibition MEK1/2 0.8
Identifier Residue Sequence Organism Cell Line
SIGNOR-244961 Homo sapiens
pmid sentence
Publications: 1 Organism: Homo Sapiens
+ MEK1/2down-regulates img/indirect_inhibition.png MEK1/2 0.621
Identifier Residue Sequence Organism Cell Line
SIGNOR-244877 Homo sapiens
pmid sentence
Pd98059, a specific inhibitor of mek in addition, immunoblot and immunostaining analysis revealed that phosphorylation of erk was increased by treatment with sb203580;whereas pd98059 increased the phosphorylation of p38, which implies a seesaw-like balance between erk and p38 phosphorylation.
Publications: 1 Organism: Homo Sapiens
Pathways:Adipogenesis, Acute Myeloid Leukemia, BCR-ABL in AML, FLT3 in AML, KIT in AML, AML_TRIPLETS, B-cell activation, COVID-19 Causal Network, Colorectal Carcinoma, EGFR Signaling, ErbB receptors in cancer, FLT3-ITD signaling, Glioblastoma Multiforme, Hepatocellular Tumor, IL6 Signaling, Insulin Signaling, Inhibition of Apoptosis, Integrin Signaling, Luminal Breast Cancer, Malignant Melanoma, NPM1_new, Noonan syndrome, Non-small-cell lung cancer (NSCLC), Oxytocin signaling, Pancreatic ductal adenocarcinoma (PDA), PI3K/AKT Signaling, Rett syndrome, Rhabdomyosarcoma, RTKs in cancer, SARS-CoV MAPK PERTURBATION, Thyroid cancer, T cell activation, Toll like receptors, VEGF Signaling
+ MAP3K1up-regulates activity img/direct-activation.png phosphorylation MEK1/2 0.648
Identifier Residue Sequence Organism Cell Line
SIGNOR-244881 Mus musculus NIH-3T3 Cell
pmid sentence
Phosphorylation at ser-218 and ser-222 by map kinase kinase kinases (raf or mekk1) positively regulates mek1 kinase activity.
Publications: 1 Organism: Mus Musculus
Pathways:COVID-19 Causal Network, EGFR Signaling, SARS-CoV MAPK PERTURBATION, Toll like receptors
+ ANXA3up-regulates activity img/indirect-activation.png MEK1/2 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-262210 Homo sapiens A-549 Cell
pmid sentence
We also investigated the potential regulation of cancer-associated signaling pathways by Anxa3 through screening for the altered expression of some common signaling molecules after Anxa3 downregulation. Decreased phosphorylation of MEK1/2, ERK1/2, Akt, and IκBα was detected after downregulating Anxa3 expression in A549 cells.
Publications: 1 Organism: Homo Sapiens
+ PPP2CAdown-regulates img/direct_inhibition.png dephosphorylation MEK1/2 0.544
Identifier Residue Sequence Organism Cell Line
SIGNOR-244941 Homo sapiens
pmid sentence
In particular, p38 mapk activity stimulates the physical association between ppa2 and mkk1/2- erk1/2 complex, leading to mkk1/2 dephosphorilation by pp2a.
Publications: 1 Organism: Homo Sapiens
Pathways:COVID-19 Causal Network, PI3K/AKT Signaling
+ 2-(2-amino-3-methoxyphenyl)chromen-4-onedown-regulates img/direct_inhibition.png chemical inhibition MEK1/2 0.8
Identifier Residue Sequence Organism Cell Line
SIGNOR-244930 Homo sapiens Neuron
pmid sentence
The mek1/2 inhibitors pd98059, sl327, and u0126 have been extensively used to implicate erk1/2 in neuroplasticity.
Publications: 1 Organism: Homo Sapiens
Tissue: Brain
+ BRAFup-regulates activity img/direct-activation.png phosphorylation MEK1/2 0.78
Identifier Residue Sequence Organism Cell Line
SIGNOR-244827 Mus musculus
pmid sentence
Activation of mek family kinases requires phosphorylation of two conserved ser/thr residueserine residues 218 and 222 of human mek1 are the primary sites for phosphorylation by c-raf.
Identifier Residue Sequence Organism Cell Line
SIGNOR-244831 in vitro
pmid sentence
Raf-1 phosphorylation of MEK activated it, as judged by its ability to stimulate the phosphorylation of myelin basic protein by glutathione S-transferase-ERK1.
Identifier Residue Sequence Organism Cell Line
SIGNOR-251988 Homo sapiens
pmid sentence
BRAFV600E has been shown to initiate thyroid follicular cell transformation. The BRAFV600E mutation disrupts the hydrophobic interaction, enabling the BRAF kinase to fold into a catalytically active formation, resulting in an almost 500-fold increase in kinase activity. Mutant BRAF can dimerize and activate MEK without Ras activation.
Publications: 3 Organism: Mus Musculus, In Vitro, Homo Sapiens
Pathways:Acute Myeloid Leukemia, BCR-ABL in AML, FLT3 in AML, KIT in AML, AML_TRIPLETS, Colorectal Carcinoma, EGFR Signaling, ErbB receptors in cancer, FLT3-ITD signaling, Glioblastoma Multiforme, Hepatocellular Tumor, IL6 Signaling, Inhibition of Apoptosis, Luminal Breast Cancer, Malignant Melanoma, NPM1_new, Noonan syndrome, Non-small-cell lung cancer (NSCLC), Pancreatic ductal adenocarcinoma (PDA), PI3K/AKT Signaling, Rett syndrome, Rhabdomyosarcoma, RTKs in cancer, Thyroid cancer, T cell activation, VEGF Signaling
+ PDPK1up-regulates activity img/direct-activation.png phosphorylation MEK1/2 0.275
Identifier Residue Sequence Organism Cell Line
SIGNOR-244934 Homo sapiens HEK-293 Cell
pmid sentence
In vitro kinase assay revealed that the direct targets of pdk1 in the mapk pathway were the upstream mapk kinases mek1 and mek2. The identified pdk1 phosphorylation sites in mek1 and mek2 are ser222 and ser226, respectively, and are known to be essential for full activation
Publications: 1 Organism: Homo Sapiens
Pathways:Adipogenesis, Acute Myeloid Leukemia, BCR-ABL in AML, FLT3 in AML, KIT in AML, B-cell activation, EGFR Signaling, ErbB receptors in cancer, FLT3-ITD signaling, Glioblastoma Multiforme, Hepatocellular Tumor, Insulin Signaling, Luminal Breast Cancer, Malignant Melanoma, Non-small-cell lung cancer (NSCLC), PI3K/AKT Signaling, Rhabdomyosarcoma, RTKs in cancer, Thyroid cancer, T cell activation, VEGF Signaling
+ LAMTOR3up-regulates img/direct-activation.png binding MEK1/2 0.604
Identifier Residue Sequence Organism Cell Line
SIGNOR-244874 Homo sapiens
pmid sentence
We analyzed the ability of mp1 to bind to mek1, erk1, and to itself, and the regulation of these interactions. Gel filtration of cell lysates revealed two major mp1 peaks: a broad high molecular weight peak and a 28 kda complex. An mp1 mutant that lost mek1 binding no longer enhanced rasv12-stimulated erk1 activity, and functioned as a dominant negative, consistent with the concept that mp1 function depends on facilitating these oligomerizations.
Publications: 1 Organism: Homo Sapiens
+ trametinibdown-regulates img/direct_inhibition.png chemical inhibition MEK1/2 0.8
Identifier Residue Sequence Organism Cell Line
SIGNOR-244871 Homo sapiens
pmid sentence
Publications: 1 Organism: Homo Sapiens
Pathways:SARS-CoV MAPK PERTURBATION
+ MEK1/2up-regulates activity img/direct-activation.png phosphorylation MAPK3 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-258991 Mus musculus
pmid sentence
Raf proteins have been shown to phosphorylate and activate MAPKKs (MAP kinase kinases) called MEKs (MAPK or ERK kinases) which in turn phosphorylate and activate MAPKs (MAP kinases) called ERKs
Publications: 1 Organism: Mus Musculus
+ BRAFup-regulates img/direct-activation.png phosphorylation MEK1/2 0.78
Identifier Residue Sequence Organism Cell Line
SIGNOR-244843 Homo sapiens
pmid sentence
We show that, consequently, b-raf interacts with mek-1 and mek-2 with a better affinity than does c-raf-1, thus strengthening the notion that b-raf is a stronger mek activator than c-raf-l.
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, BCR-ABL in AML, FLT3 in AML, KIT in AML, AML_TRIPLETS, Colorectal Carcinoma, EGFR Signaling, ErbB receptors in cancer, FLT3-ITD signaling, Glioblastoma Multiforme, Hepatocellular Tumor, IL6 Signaling, Inhibition of Apoptosis, Luminal Breast Cancer, Malignant Melanoma, NPM1_new, Noonan syndrome, Non-small-cell lung cancer (NSCLC), Pancreatic ductal adenocarcinoma (PDA), PI3K/AKT Signaling, Rett syndrome, Rhabdomyosarcoma, RTKs in cancer, Thyroid cancer, T cell activation, VEGF Signaling
+ PDCD1down-regulates activity img/indirect_inhibition.png MEK1/2 0.268
Identifier Residue Sequence Organism Cell Line
SIGNOR-275410 Homo sapiens T-lymphocyte
pmid sentence
MEK1/2 was phosphorylated and activated upon activation of T cells through TCR-CD3 and CD28, which resulted in phosphorylation of its downstream target ERK1/2, as determined by Western blotting analysis with an antibody specific for ERK1/2 phosphorylated at Thr202 and Tyr204, markers of activation. PD-1 substantially inhibited the activation of MEK1/2 and ERK1/2
Publications: 1 Organism: Homo Sapiens
+ ARAFup-regulates img/direct-activation.png phosphorylation MEK1/2 0.744
Identifier Residue Sequence Organism Cell Line
SIGNOR-244809 Homo sapiens
pmid sentence
Active raf phosphorylates mek.
Identifier Residue Sequence Organism Cell Line
SIGNOR-244813 Homo sapiens HeLa Cell
pmid sentence
Our data demonstrated that a-raf is, indeed, a mek1 activator and may play a role in growth factor signaling.
Publications: 2 Organism: Homo Sapiens
Pathways:EGFR Signaling
+ WDR83up-regulates img/direct-activation.png binding MEK1/2 0.516
Identifier Residue Sequence Organism Cell Line
SIGNOR-244964 Homo sapiens
pmid sentence
Morg1 specifically associates with several components of the erk pathway, including mp1, raf-1, mek, and erk, and stabilizes their assembly into an oligomeric complex.
Publications: 1 Organism: Homo Sapiens
+ PD318088down-regulates img/direct_inhibition.png chemical inhibition MEK1/2 0.8
Identifier Residue Sequence Organism Cell Line
SIGNOR-244927 Homo sapiens
pmid sentence
Publications: 1 Organism: Homo Sapiens
+ CDK1down-regulates img/direct_inhibition.png phosphorylation MEK1/2 0.478
Identifier Residue Sequence Organism Cell Line
SIGNOR-244847 Homo sapiens
pmid sentence
P34cdc2 catalyzes the in vitro phosphorylation of mkk1 on both of these threonine residues and inactivates mkk1 enzymatic activity. Both sites are phosphorylated in vivo as well
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, KIT in AML
+ MAP3K8up-regulates img/direct-activation.png phosphorylation MEK1/2 0.559
Identifier Residue Sequence Organism Cell Line
SIGNOR-244892 Homo sapiens
pmid sentence
Activation of mek family kinases requires phosphorylation of two conserved ser/thr residues.Phosphopeptide analysis demonstrated that serine residues 218 and 222 of human mek1 are the primary sites for phosphorylation by c-raf
Identifier Residue Sequence Organism Cell Line
SIGNOR-244904 Homo sapiens HEK-293 Cell
pmid sentence
Cot proteins were used in an in vitro kinase assay using mek as a substrate. Samples were analyzed by western blotting. As seen in the cascade activity assay only wild-type cot was active against mekregulation of cot is of great interest to the signaling field since the cot/mek/erk pathway potentially plays a role in the etiology of inflammatory autoimmune diseases.
Publications: 2 Organism: Homo Sapiens
Pathways:Toll like receptors
+ FGFR2up-regulates img/indirect-activation.png MEK1/2 0.306
Identifier Residue Sequence Organism Cell Line
SIGNOR-244868 Mus musculus 3T3-L1 Cell
pmid sentence
Fibroblast growth factor-2 (FGF-2), in the presence of dexamethasone, isobutylmethylxanthine, and insulin, induces a prolonged activation of the MEK/ERK signaling pathway, which lasts for at least 12 h post-induction, and this activity is less sensitive to the MEK inhibitors
Publications: 1 Organism: Mus Musculus
+ RAF1up-regulates activity img/direct-activation.png phosphorylation MEK1/2 0.739
Identifier Residue Sequence Organism Cell Line
SIGNOR-244945 Homo sapiens
pmid sentence
The best characterized Raf substrates are MEK1 and MEK2. The activation of MEK1/2 by Raf is required to mediate many of the cellular responses to Raf activation, suggesting that MEK1/2 are the dominant Raf effector proteins.
Publications: 1 Organism: Homo Sapiens
Tissue: Ovary
Pathways:Adipogenesis, COVID-19 Causal Network, Insulin Signaling, Integrin Signaling, Noonan syndrome, Oxytocin signaling, SARS-CoV MAPK PERTURBATION
+ MEK1/2down-regulates activity img/direct_inhibition.png phosphorylation CASP9 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-270222
pmid sentence
Inhibition of caspase-9 through phosphorylation at Thr 125 by ERK MAPK|The opposing protein kinase activity is overcome by treatment with the broad-specificity kinase inhibitor staurosporine or with inhibitors of MEK1/2
Publications: 1
Pathways:COVID-19 Causal Network, Inhibition of Apoptosis
+ MAPK14down-regulates activity img/indirect_inhibition.png MEK1/2 0.662
Identifier Residue Sequence Organism Cell Line
SIGNOR-263511 Homo sapiens Skin Fibroblast
pmid sentence
Activation of p38 MAPK is required for arsenite-induced apoptosis and MEK1,2 dephosphorylation in human skin fibroblasts. Our data suggest the presence of a continuous negative feedback from p38α and p38β to MEK1,2 as simultaneous inhibition of p38α and p38β isoforms in normal quiescent cells resulted in accumulation of phosphorylated MEK1,2 (Fig. 2A) ⇓ . This negative regulation of MEK1,2 in normal cells could be considered a means to control MEK1,2-mediated proliferation and expression of transformation-related genes.
Publications: 1 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling, Toll like receptors
+ FGFR1up-regulates img/indirect-activation.png MEK1/2 0.315
Identifier Residue Sequence Organism Cell Line
SIGNOR-244865 Homo sapiens
pmid sentence
Fibroblast growth factor-2 (FGF-2), in the presence of dexamethasone, isobutylmethylxanthine, and insulin, induces a prolonged activation of the MEK/ERK signaling pathway, which lasts for at least 12 h post-induction, and this activity is less sensitive to the MEK inhibitors
Publications: 1 Organism: Homo Sapiens
Pathways:Luminal Breast Cancer
+ MEK1/2up-regulates quantity by expression img/indirect-activation.png transcriptional regulation CEBPA 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-244773 Mus musculus 3T3-L1 Cell
pmid sentence
We further show that activation of mek1 significantly enhances the transactivation of the c/ebpalpha minimal promoter during the early phase of the differentiation process.
Publications: 1 Organism: Mus Musculus
Pathways:Adipogenesis, Acute Myeloid Leukemia, FLT3 in AML, AML_TRIPLETS, NPM1_new
+ MEK1/2up-regulates activity img/direct-activation.png phosphorylation ERK1/2 0.749
Identifier Residue Sequence Organism Cell Line
SIGNOR-258989 Mus musculus
pmid sentence
Raf proteins have been shown to phosphorylate and activate MAPKKs (MAP kinase kinases) called MEKs (MAPK or ERK kinases) which in turn phosphorylate and activate MAPKs (MAP kinases) called ERKs
Publications: 1 Organism: Mus Musculus
Pathways:Adipogenesis, Acute Myeloid Leukemia, BCR-ABL in AML, FLT3 in AML, KIT in AML, AML_TRIPLETS, B-cell activation, COVID-19 Causal Network, Colorectal Carcinoma, EGFR Signaling, ErbB receptors in cancer, FLT3-ITD signaling, Glioblastoma Multiforme, Hepatocellular Tumor, IL6 Signaling, Insulin Signaling, Inhibition of Apoptosis, Integrin Signaling, Luminal Breast Cancer, Malignant Melanoma, NPM1_new, Noonan syndrome, Non-small-cell lung cancer (NSCLC), Oxytocin signaling, Pancreatic ductal adenocarcinoma (PDA), PI3K/AKT Signaling, Rett syndrome, Rhabdomyosarcoma, RTKs in cancer, SARS-CoV MAPK PERTURBATION, Thyroid cancer, T cell activation, Toll like receptors, VEGF Signaling
+ MEK1/2up-regulates img/direct-activation.png binding PPARG 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-244971 Homo sapiens
pmid sentence
The genomic activity of ppargamma is modulated, in addition to ligand binding, by phosphorylation of a serine residue by mapks, such as extracellular signal-regulated protein kinases-1/2 (erk-1/2), or by nucleocytoplasmic compartmentalization through the erk activators mapk kinases-1/2 (mek-1/2). These mapks phosphorylate (in humans) ser 84 in the ppargamma1 and ser 114 in ppargamma2 isoform.
Publications: 1 Organism: Homo Sapiens
Pathways:Adipogenesis, Rett syndrome, Thyroid cancer
+ MAP3K2up-regulates img/direct-activation.png phosphorylation MEK1/2 0.422
Identifier Residue Sequence Organism Cell Line
SIGNOR-244888 Homo sapiens
pmid sentence
Both mekk2 and mekk3 are able to activate the jun kinase pathway in vivo. However, following routine immunoprecipitation in triton x-100, mekk2 but not mekk3 is able to effectively phosphorylate both sek-1 and mek-1 and to undergo autophosphorylation
Publications: 1 Organism: Homo Sapiens
+ 2-(2-chloro-4-iodoanilino)-N-(cyclopropylmethoxy)-3,4-difluorobenzamidedown-regulates img/direct_inhibition.png chemical inhibition MEK1/2 0.8
Identifier Residue Sequence Organism Cell Line
SIGNOR-244854 Homo sapiens
pmid sentence
Publications: 1 Organism: Homo Sapiens
+ MAPK1down-regulates activity img/direct_inhibition.png phosphorylation MEK1/2 0.745
Identifier Residue Sequence Organism Cell Line
SIGNOR-244912 Homo sapiens HEK-293 Cell
pmid sentence
An ERK2-binding site at the N terminus of MEK1 was reported to mediate their stable association. We examined the importance of this binding site in the feedback phosphorylation of mek1 on thr(292) and thr(386) by erk2
Identifier Residue Sequence Organism Cell Line
SIGNOR-244916 Chlorocebus aethiops COS Cell
pmid sentence
We propose that activation of erk during adhesion creates a feedback system in which erk phosphorylates mek1 on t292, and this in turn blocks additional s298 phosphorylation in response to integrin signaling.
Publications: 2 Organism: Homo Sapiens, Chlorocebus Aethiops
+ selumetinibdown-regulates img/direct_inhibition.png chemical inhibition MEK1/2 0.8
Identifier Residue Sequence Organism Cell Line
SIGNOR-244823 Homo sapiens
pmid sentence
Publications: 1 Organism: Homo Sapiens
Pathways:SARS-CoV MAPK PERTURBATION
+ MEK1/2up-regulates quantity by expression img/indirect-activation.png transcriptional regulation CHEK1 0.2
Identifier Residue Sequence Organism Cell Line
SIGNOR-263069 Homo sapiens
pmid sentence
Mechanistically, Ras-MEK signaling drives Chk1 expression and promotes cancer cell growth that produces genotoxic stress that requires Chk1 to mediate a response to the consequent DNA damage. Reciprocally, Chk1 engages a negative feedback loop to prevent hyperactivation of Ras-MEK signaling, thereby limiting DNA damage. Ras–MEK signaling transcriptionally activates Chk1, which appears to sustain cancer cell growth by maintaining DNA damage levels below a threshold that would otherwise drive apoptosis.
Publications: 1 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling
+ trametinibdown-regulates activity img/direct_inhibition.png chemical inhibition MEK1/2 0.8
Identifier Residue Sequence Organism Cell Line
SIGNOR-262312 Homo sapiens HuH-7 Cell
pmid sentence
Inhibitors of MEK1/2 (trametinib) and/or ERK1/2 (selumetinib) had the strongest and most conserved inhibitory activities, suggesting that MEK1/2 and ERK1/2 may have unique capabilities as stand-alone or combinatorial therapies for MERS-CoV infections. 
Identifier Residue Sequence Organism Cell Line
SIGNOR-259446 Homo sapiens
pmid sentence
Trametinib (Mekinist™) is a reversible and highly selective allosteric inhibitor of MEK1 and MEK2 with anticancer activity against metastatic melanoma carrying the BRAF V600 mutation.
Publications: 2 Organism: Homo Sapiens
Pathways:SARS-CoV MAPK PERTURBATION
+ PDPK1up-regulates img/direct-activation.png phosphorylation MEK1/2 0.275
Identifier Residue Sequence Organism Cell Line
SIGNOR-244938 Homo sapiens
pmid sentence
The identified pdk1 phosphorylation sites in mek1 and mek2 are ser222 and ser226, respectively, and are known to be essential for full activation.
Publications: 1 Organism: Homo Sapiens
Pathways:Adipogenesis, Acute Myeloid Leukemia, BCR-ABL in AML, FLT3 in AML, KIT in AML, B-cell activation, EGFR Signaling, ErbB receptors in cancer, FLT3-ITD signaling, Glioblastoma Multiforme, Hepatocellular Tumor, Insulin Signaling, Luminal Breast Cancer, Malignant Melanoma, Non-small-cell lung cancer (NSCLC), PI3K/AKT Signaling, Rhabdomyosarcoma, RTKs in cancer, Thyroid cancer, T cell activation, VEGF Signaling
+ RAF1up-regulates img/direct-activation.png phosphorylation MEK1/2 0.739
Identifier Residue Sequence Organism Cell Line
SIGNOR-244952 Homo sapiens
pmid sentence
The best characterized Raf substrates are MEK1 and MEK2. The activation of MEK1/2 by Raf is required to mediate many of the cellular responses to Raf activation, suggesting that MEK1/2 are the dominant Raf effector proteins.
Publications: 1 Organism: Homo Sapiens
Pathways:Adipogenesis, COVID-19 Causal Network, Insulin Signaling, Integrin Signaling, Noonan syndrome, Oxytocin signaling, SARS-CoV MAPK PERTURBATION
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