MAPK8 - Wiki-MPM

Interactant Symbol	Name	Associated Pathways Hide	Binding Drugs Hide	Associated Diseases Hide
AKT1	AKT serine/threonine kinase 1	Activation of BAD and translocation to mitochondria PIP3 activates AKT signaling PIP3 activates AKT signaling Downregulation of ERBB2:ERBB3 signaling Translocation of SLC2A4 (GLUT4) to the plasma membrane Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation MTOR signalling AKT phosphorylates targets in the cytosol AKT phosphorylates targets in the cytosol AKT phosphorylates targets in the nucleus Negative regulation of the PI3K/AKT network eNOS activation AKT-mediated inactivation of FOXO1A Integrin signaling Deactivation of the beta-catenin transactivating complex CD28 dependent PI3K/Akt signaling CTLA4 inhibitory signaling G beta:gamma signalling through PI3Kgamma Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA KSRP (KHSRP) binds and destabilizes mRNA VEGFR2 mediated vascular permeability TP53 Regulates Metabolic Genes Constitutive Signaling by AKT1 E17K in Cancer Interleukin-4 and Interleukin-13 signaling Regulation of TP53 Degradation Regulation of TP53 Activity through Acetylation Regulation of TP53 Activity through Association with Co-factors PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling Cyclin E associated events during G1/S transition Cyclin A:Cdk2-associated events at S phase entry PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 RAB GEFs exchange GTP for GDP on RABs RUNX2 regulates genes involved in cell migration Regulation of PTEN stability and activity Extra-nuclear estrogen signaling Negative regulation of NOTCH4 signaling FLT3 Signaling Regulation of localization of FOXO transcription factors Estrogen-dependent nuclear events downstream of ESR-membrane signaling	ATP Arsenic trioxide Genistein Inositol 1,3,4,5-Tetrakisphosphate Resveratrol Archexin Enzastaurin Perifosine N-[2-(5-methyl-4H-1,2,4-triazol-3-yl)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine 5-(5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine	PTEN hamartoma tumor syndrome (PHTS), including: Cowden syndrome; Bannayan-Riley-Ruvalcaba syndrome; Proteus syndrome; Proteus-like syndrome
MAPK3	mitogen-activated protein kinase 3	MAPK3 (ERK1) activation RAF-independent MAPK1/3 activation ISG15 antiviral mechanism Spry regulation of FGF signaling Frs2-mediated activation ERK/MAPK targets ERK/MAPK targets ERKs are inactivated Regulation of actin dynamics for phagocytic cup formation Oxidative Stress Induced Senescence Senescence-Associated Secretory Phenotype (SASP) Oncogene Induced Senescence Oncogene Induced Senescence FCERI mediated MAPK activation Regulation of HSF1-mediated heat shock response NCAM signaling for neurite out-growth RSK activation Signal transduction by L1 Activation of the AP-1 family of transcription factors Thrombin signalling through proteinase activated receptors (PARs) Negative regulation of FGFR1 signaling Negative regulation of FGFR2 signaling Negative regulation of FGFR3 signaling Negative regulation of FGFR4 signaling RHO GTPases Activate WASPs and WAVEs RHO GTPases Activate NADPH Oxidases RAF/MAP kinase cascade MAP2K and MAPK activation Negative feedback regulation of MAPK pathway Negative regulation of MAPK pathway Signaling by moderate kinase activity BRAF mutants Signaling by high-kinase activity BRAF mutants Signaling by BRAF and RAF fusions Paradoxical activation of RAF signaling by kinase inactive BRAF PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling RNA Polymerase I Promoter Opening Signal attenuation Advanced glycosylation endproduct receptor signaling Gastrin-CREB signalling pathway via PKC and MAPK ESR-mediated signaling RUNX2 regulates osteoblast differentiation Regulation of PTEN gene transcription Regulation of the apoptosome activity Estrogen-dependent nuclear events downstream of ESR-membrane signaling Suppression of apoptosis Signaling downstream of RAS mutants Signaling by MAP2K mutants Signaling by RAF1 mutants FCGR3A-mediated phagocytosis Growth hormone receptor signaling	Sulindac Acetylsalicylic acid Minocycline Arsenic trioxide Purvalanol 5-iodotubercidin Seliciclib Cholecystokinin Ulixertinib
RAF1	Raf-1 proto-oncogene, serine/threonine kinase	Stimuli-sensing channels Rap1 signalling GP1b-IX-V activation signalling CD209 (DC-SIGN) signaling RAF activation MAP2K and MAPK activation Negative feedback regulation of MAPK pathway Negative regulation of MAPK pathway Signaling by moderate kinase activity BRAF mutants Signaling by high-kinase activity BRAF mutants Signaling by BRAF and RAF fusions Paradoxical activation of RAF signaling by kinase inactive BRAF Signaling downstream of RAS mutants Signaling by RAF1 mutants Signaling by MRAS-complex mutants	Sorafenib LErafAON XL281 iCo-007 Cholecystokinin Regorafenib Dabrafenib Fostamatinib
TP53	tumor protein p53	Activation of NOXA and translocation to mitochondria Activation of PUMA and translocation to mitochondria Pre-NOTCH Transcription and Translation Oxidative Stress Induced Senescence Formation of Senescence-Associated Heterochromatin Foci (SAHF) Oncogene Induced Senescence DNA Damage/Telomere Stress Induced Senescence SUMOylation of transcription factors Autodegradation of the E3 ubiquitin ligase COP1 Association of TriC/CCT with target proteins during biosynthesis TP53 Regulates Metabolic Genes Ub-specific processing proteases Ovarian tumor domain proteases Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks Interleukin-4 and Interleukin-13 signaling TP53 Regulates Transcription of DNA Repair Genes TP53 Regulates Transcription of Genes Involved in Cytochrome C Release TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain TP53 Regulates Transcription of Caspase Activators and Caspases TP53 Regulates Transcription of Death Receptors and Ligands TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest Regulation of TP53 Expression Regulation of TP53 Activity through Phosphorylation Regulation of TP53 Degradation Regulation of TP53 Activity through Acetylation Regulation of TP53 Activity through Association with Co-factors Regulation of TP53 Activity through Methylation PI5P Regulates TP53 Acetylation G2/M DNA damage checkpoint G2/M Checkpoints Stabilization of p53 Transcriptional activation of cell cycle inhibitor p21 The role of GTSE1 in G2/M progression after G2 checkpoint Transcriptional Regulation by VENTX RUNX3 regulates CDKN1A transcription Regulation of PTEN gene transcription Regulation of PTEN gene transcription Factors involved in megakaryocyte development and platelet production	Acetylsalicylic acid Zinc Triethyl phosphate AZD 3355 1-(9-ethyl-9H-carbazol-3-yl)-N-methylmethanamine Zinc acetate Zinc chloride Zinc sulfate, unspecified form	Osteosarcoma Adrenal carcinoma Thyroid cancer Breast cancer Basal cell carcinoma Malignant melanoma Pancreatic cancer Gastric cancer Malignant pleural mesothelioma Non-small cell lung cancer Esophageal cancer Oral cancer Multiple myeloma Small cell lung cancer Li-Fraumeni syndrome, including: Classic Li-Fraumeni syndrome (LFS); LFS-like syndrome (LFSL) Glioma Squamous cell carcinoma Kaposi's sarcoma Cholangiocarcinoma Gallbladder cancer Cancer of the anal canal Hepatocellular carcinoma Choriocarcinoma Vulvar cancer Choroid plexus papilloma Burkitt lymphoma Adult T-cell leukemia Hairy-cell leukemia Bladder cancer Chronic lymphocytic leukemia (CLL) Penile cancer Endometrial Cancer Ovarian cancer Colorectal cancer Laryngeal cancer Chronic myeloid leukemia (CML)
JUN	Jun proto-oncogene, AP-1 transcription factor subunit	Pre-NOTCH Transcription and Translation Oxidative Stress Induced Senescence Senescence-Associated Secretory Phenotype (SASP) FCERI mediated MAPK activation Activation of the AP-1 family of transcription factors Activation of anterior HOX genes in hindbrain development during early embryogenesis MAPK6/MAPK4 signaling TP53 Regulates Transcription of DNA Repair Genes Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models Regulation of PTEN gene transcription Regulation of PTEN gene transcription Estrogen-dependent gene expression WNT5:FZD7-mediated leishmania damping	Adapalene Vinblastine Pseudoephedrine Irbesartan Arsenic trioxide LGD-1550
HRAS	HRas proto-oncogene, GTPase	SOS-mediated signalling Activation of RAS in B cells Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants SHC1 events in ERBB2 signaling SHC1 events in ERBB4 signaling Signaling by SCF-KIT Signalling to RAS p38MAPK events p38MAPK events GRB2 events in EGFR signaling SHC1 events in EGFR signaling Downstream signal transduction GRB2 events in ERBB2 signaling GRB2 events in ERBB2 signaling Tie2 Signaling EGFR Transactivation by Gastrin DAP12 signaling SHC-related events triggered by IGF1R FCERI mediated MAPK activation NCAM signaling for neurite out-growth EPHB-mediated forward signaling Ras activation upon Ca2+ influx through NMDA receptor VEGFR2 mediated cell proliferation CD209 (DC-SIGN) signaling Constitutive Signaling by EGFRvIII SHC-mediated cascade:FGFR1 FRS-mediated FGFR1 signaling SHC-mediated cascade:FGFR2 FRS-mediated FGFR2 signaling SHC-mediated cascade:FGFR3 FRS-mediated FGFR3 signaling FRS-mediated FGFR4 signaling SHC-mediated cascade:FGFR4 Signaling by FGFR2 in disease Signaling by FGFR4 in disease Signaling by FGFR1 in disease Regulation of RAS by GAPs RAF activation RAF/MAP kinase cascade MAP2K and MAPK activation Negative regulation of MAPK pathway Signaling by moderate kinase activity BRAF mutants Signaling by high-kinase activity BRAF mutants Signaling by BRAF and RAF fusions RAS signaling downstream of NF1 loss-of-function variants Paradoxical activation of RAF signaling by kinase inactive BRAF Insulin receptor signalling cascade PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases MET activates RAS signaling Signaling by FGFR3 fusions in cancer Signaling by FGFR3 point mutants in cancer Activated NTRK2 signals through RAS Erythropoietin activates RAS Activated NTRK2 signals through FRS2 and FRS3 Activated NTRK3 signals through RAS FLT3 Signaling Constitutive Signaling by Overexpressed ERBB2 Estrogen-stimulated signaling through PRKCZ RAS processing RAS GTPase cycle mutants Signaling downstream of RAS mutants Signaling by RAF1 mutants Signaling by ERBB2 KD Mutants Signaling by ERBB2 ECD mutants Signaling by ERBB2 TMD/JMD mutants Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants Signaling by PDGFRA extracellular domain mutants Signaling by FLT3 fusion proteins Signaling by FLT3 ITD and TKD mutants	Hexane-1,6-Diol Trifluoroethanol Guanosine-5'-Triphosphate Guanosine-5'-Diphosphate N,N'-DIMETHYL-N-(ACETYL)-N'-(7-NITROBENZ-2-OXA-1,3-DIAZOL-4-YL)ETHYLENEDIAMINE	Bladder cancer Penile cancer Squamous cell carcinoma Thyroid cancer Cervical cancer Hepatocellular carcinoma Noonan syndrome and related disorders, including: Noonan syndrome (NS); Leopard syndrome (LS); Noonan syndrome-like with loose anagen hair (NS/LAH); CBL-mutation associated syndrome (CBL); Neurofibromatosis type 1 (NF1); Neurofibromatosis type 2 (NF2); Neurofibromatosis-Noonan syndrome (NFNS); Legius syndrome; Cardiofaciocutaneous syndrome (CFCS); Costello syndrome (CS)
MAP2K2	mitogen-activated protein kinase kinase 2	MAPK1 (ERK2) activation Frs2-mediated activation Signal transduction by L1 Uptake and function of anthrax toxins RAF activation MAP2K and MAPK activation Negative feedback regulation of MAPK pathway Signaling by moderate kinase activity BRAF mutants Signaling by high-kinase activity BRAF mutants Signaling by BRAF and RAF fusions Paradoxical activation of RAF signaling by kinase inactive BRAF Signaling downstream of RAS mutants Signaling by MAP2K mutants Signaling by RAF1 mutants	Bosutinib Trametinib Selumetinib Binimetinib Fostamatinib	Noonan syndrome and related disorders, including: Noonan syndrome (NS); Leopard syndrome (LS); Noonan syndrome-like with loose anagen hair (NS/LAH); CBL-mutation associated syndrome (CBL); Neurofibromatosis type 1 (NF1); Neurofibromatosis type 2 (NF2); Neurofibromatosis-Noonan syndrome (NFNS); Legius syndrome; Cardiofaciocutaneous syndrome (CFCS); Costello syndrome (CS)
MAPK8IP1	mitogen-activated protein kinase 8 interacting protein 1		Pyrazolanthrone 6-CHLORO-9-HYDROXY-1,3-DIMETHYL-1,9-DIHYDRO-4H-PYRAZOLO[3,4-B]QUINOLIN-4-ONE N-(4-AMINO-5-CYANO-6-ETHOXYPYRIDIN-2-YL)-2-(4-BROMO-2,5-DIMETHOXYPHENYL)ACETAMIDE 5-CYANO-N-(2,5-DIMETHOXYBENZYL)-6-ETHOXYPYRIDINE-2-CARBOXAMIDE Anthralin
MAPT	microtubule associated protein tau	Caspase-mediated cleavage of cytoskeletal proteins	Lansoprazole Astemizole Paclitaxel Docetaxel Flortaucipir F-18	Amyotrophic lateral sclerosis (ALS); Lou Gehrig's disease Frontotemporal lobar degeneration (FTLD), including: Pick disease of brain; Frontotemporal dementia (FTD); Ubiquitin-positive frontotemporal dementia (UP-FTD); Progressive supranuclear palsy type 1 (PSNP1); Inclusion body myopathy with early-onset paget disease and frontotemporal dementia (IBMPFD); Frontotemporal dementia, chromosome 3-linked (FTD3) Progressive supranuclear palsy (PSP); Steele-Richardson-Olszewski syndrome
APLP2	amyloid beta precursor like protein 2	Platelet degranulation Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) Post-translational protein phosphorylation	Zinc Zinc acetate Zinc chloride Zinc sulfate, unspecified form
HSPA8	heat shock protein family A (Hsp70) member 8	Regulation of HSF1-mediated heat shock response HSP90 chaperone cycle for steroid hormone receptors (SHR) Attenuation phase HSF1-dependent transactivation Lysosome Vesicle Biogenesis Golgi Associated Vesicle Biogenesis CHL1 interactions AUF1 (hnRNP D0) binds and destabilizes mRNA Interleukin-4 and Interleukin-13 signaling Neutrophil degranulation mRNA Splicing - Major Pathway Clathrin-mediated endocytosis Protein methylation GABA synthesis, release, reuptake and degradation Lipophagy Chaperone Mediated Autophagy Late endosomal microautophagy	Dasatinib (2R,3R,4S,5R)-2-[6-amino-8-[(3,4-dichlorophenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Copper Artenimol
PIK3R1	phosphoinositide-3-kinase regulatory subunit 1	PI3K Cascade IRS-mediated signalling GPVI-mediated activation cascade Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants PI3K events in ERBB4 signaling PIP3 activates AKT signaling Interleukin-7 signaling Interleukin-7 signaling Signaling by SCF-KIT Synthesis of PIPs at the plasma membrane GAB1 signalosome Signaling by cytosolic FGFR1 fusion mutants Downstream signal transduction PI3K events in ERBB2 signaling PI3K/AKT activation Downstream TCR signaling Role of phospholipids in phagocytosis Tie2 Signaling Constitutive Signaling by Aberrant PI3K in Cancer DAP12 signaling Role of LAT2/NTAL/LAB on calcium mobilization Nephrin family interactions Costimulation by the CD28 family CD28 dependent PI3K/Akt signaling G alpha (q) signalling events GP1b-IX-V activation signalling VEGFA-VEGFR2 Pathway VEGFA-VEGFR2 Pathway Interleukin-3, Interleukin-5 and GM-CSF signaling Constitutive Signaling by EGFRvIII PI-3K cascade:FGFR1 PI-3K cascade:FGFR2 PI-3K cascade:FGFR3 PI-3K cascade:FGFR4 Signaling by FGFR2 in disease Signaling by FGFR4 in disease Signaling by FGFR1 in disease RAF/MAP kinase cascade Interleukin-4 and Interleukin-13 signaling PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling MET activates PI3K/AKT signaling Signaling by FGFR3 fusions in cancer Signaling by FGFR3 point mutants in cancer RET signaling Extra-nuclear estrogen signaling Erythropoietin activates Phosphoinositide-3-kinase (PI3K) Erythropoietin activates Phosphoinositide-3-kinase (PI3K) Activated NTRK2 signals through PI3K Interleukin receptor SHC signaling Regulation of signaling by CBL Regulation of signaling by CBL Activated NTRK3 signals through PI3K FLT3 Signaling FLT3 Signaling Signaling by ERBB2 KD Mutants Signaling by ERBB2 ECD mutants Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants Signaling by PDGFRA extracellular domain mutants Signaling by FLT3 fusion proteins Signaling by FLT3 fusion proteins Signaling by FLT3 ITD and TKD mutants Signaling by FLT3 ITD and TKD mutants Antigen activates B Cell Receptor (BCR) leading to generation of second messengers Antigen activates B Cell Receptor (BCR) leading to generation of second messengers	Isoprenaline SF1126 Enzastaurin Wortmannin
TNFSF11	TNF superfamily member 11	TNFR2 non-canonical NF-kB pathway TNFs bind their physiological receptors TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway	Lenalidomide AMGN-0007 Denosumab Thiocolchicoside	Osteopetrosis, including: Osteopetrosis, severe neonatal or infantile forms; Osteopetrosis, intermediate forms; Osteopetrosis with renal tubular acidosis; Osteopetrosis, late-onset form type 1; Osteopetrosis, late-onset form type 2; Osteopetrosis, osteoclast poor
TP73	tumor protein p73	Activation of PUMA and translocation to mitochondria TP53 Regulates Transcription of Genes Involved in Cytochrome C Release TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain TP53 Regulates Transcription of Caspase Activators and Caspases TP53 Regulates Transcription of Death Receptors and Ligands Regulation of TP53 Activity through Association with Co-factors RUNX1 regulates transcription of genes involved in differentiation of HSCs	Zinc Zinc acetate Zinc chloride Zinc sulfate, unspecified form	Hepatocellular carcinoma
BCL2L1	BCL2 like 1	BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members Interleukin-4 and Interleukin-13 signaling The NLRP1 inflammasome RAS processing STAT5 activation downstream of FLT3 ITD mutants	4'-FLUORO-1,1'-BIPHENYL-4-CARBOXYLIC ACID Isosorbide Gossypol
HDAC9	histone deacetylase 9	NOTCH1 Intracellular Domain Regulates Transcription Constitutive Signaling by NOTCH1 PEST Domain Mutants Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants Notch-HLH transcription pathway	Valproic acid Belinostat Panobinostat
KRT8	keratin 8	Keratinization Formation of the cornified envelope	Tenecteplase Lanoteplase Copper
SIRT1	sirtuin 1	Regulation of HSF1-mediated heat shock response Circadian Clock SIRT1 negatively regulates rRNA expression SIRT1 negatively regulates rRNA expression Regulation of FOXO transcriptional activity by acetylation Regulation of FOXO transcriptional activity by acetylation	Resveratrol Selisistat Cambinol
BMPR2	bone morphogenetic protein receptor type 2	Signaling by BMP	Dibotermin alfa Fostamatinib
HSD17B4	hydroxysteroid 17-beta dehydrogenase 4	Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol alpha-linolenic acid (ALA) metabolism Beta-oxidation of pristanoyl-CoA Beta-oxidation of very long chain fatty acids Peroxisomal protein import Peroxisomal protein import TYSND1 cleaves peroxisomal proteins	NADH (R)-3-hydroxydecanoyl-CoA	Peroxisomal beta-oxidation enzyme deficiency, including: Acyl-CoA oxidase (ACOX) deficiency; D-bifunctional protein (DBP) deficiency; Perrault syndrome; Sterol carrier protein X (SCPx) deficiency; 2-Methylacyl-CoA racemase (AMCR) deficiency; Hypercholanemia

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