RGD Reference Report - MEK kinases are regulated by EGF and selectively interact with Rac/Cdc42. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources
Advanced Search (OLGA)

MEK kinases are regulated by EGF and selectively interact with Rac/Cdc42.

Authors: Fanger, GR  Johnson, NL  Johnson, GL 
Citation: Fanger GR, etal., EMBO J. 1997 Aug 15;16(16):4961-72.
RGD ID: 2293879
Pubmed: PMID:9305638   (View Abstract at PubMed)
PMCID: PMC1170131   (View Article at PubMed Central)
DOI: DOI:10.1093/emboj/16.16.4961   (Journal Full-text)

MEK kinases (MEKKs) 1, 2, 3 and 4 are members of sequential kinase pathways that regulate MAP kinases including c-Jun NH2-terminal kinases (JNKs) and extracellular regulated kinases (ERKs). Confocal immunofluorescence microscopy of COS cells demonstrated differential MEKK subcellular localization: MEKK1 was nuclear and in post-Golgi vesicular-like structures; MEKK2 and 4 were localized to distinct Golgi-associated vesicles that were dispersed by brefeldin A. MEKK1 and 2 were activated by EGF, and kinase-inactive mutants of each MEKK partially inhibited EGF-stimulated JNK activity. Kinase-inactive MEKK1, but not MEKK2, 3 or 4, strongly inhibited EGF-stimulated ERK activity. In contrast to MEKK2 and 3, MEKK1 and 4 specifically associated with Rac and Cdc42 and kinase-inactive mutants blocked Rac/Cdc42 stimulation of JNK activity. Inhibitory mutants of MEKK1-4 did not affect p21-activated kinase (PAK) activation of JNK, indicating that the PAK-regulated JNK pathway is independent of MEKKs. Thus, in different cellular locations, specific MEKKs are required for the regulation of MAPK family members, and MEKK1 and 4 are involved in the regulation of JNK activation by Rac/Cdc42 independent of PAK. Differential MEKK subcellular distribution and interaction with small GTP-binding proteins provides a mechanism to regulate MAP kinase responses in localized regions of the cell and to different upstream stimuli.



Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations


  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CDC42Humanc-Jun N-terminal kinases MAPK signaling pathway   IMP  RGD 
Cdc42Ratc-Jun N-terminal kinases MAPK signaling pathway   ISOCDC42 (Homo sapiens) RGD 
Cdc42Mousec-Jun N-terminal kinases MAPK signaling pathway   ISOCDC42 (Homo sapiens) RGD 
MAP3K1Humanc-Jun N-terminal kinases MAPK signaling pathway   IMP  RGD 
MAP3K2Humanc-Jun N-terminal kinases MAPK signaling pathway   IMP  RGD 
MAP3K3Humanc-Jun N-terminal kinases MAPK signaling pathway   IMP  RGD 
MAP3K4Humanc-Jun N-terminal kinases MAPK signaling pathway   IMP  RGD 
Map3k1Mousec-Jun N-terminal kinases MAPK signaling pathway   ISOMAP3K1 (Homo sapiens) RGD 
Map3k1Ratc-Jun N-terminal kinases MAPK signaling pathway   ISOMAP3K1 (Homo sapiens) RGD 
Map3k2Ratc-Jun N-terminal kinases MAPK signaling pathway   ISOMAP3K2 (Homo sapiens) RGD 
Map3k2Mousec-Jun N-terminal kinases MAPK signaling pathway   ISOMAP3K2 (Homo sapiens) RGD 
Map3k3Ratc-Jun N-terminal kinases MAPK signaling pathway   ISOMAP3K3 (Homo sapiens) RGD 
Map3k3Mousec-Jun N-terminal kinases MAPK signaling pathway   ISOMAP3K3 (Homo sapiens) RGD 
Map3k4Ratc-Jun N-terminal kinases MAPK signaling pathway   ISOMAP3K4 (Homo sapiens) RGD 
Map3k4Mousec-Jun N-terminal kinases MAPK signaling pathway   ISOMAP3K4 (Homo sapiens) RGD 
RAC1Humanc-Jun N-terminal kinases MAPK signaling pathway   IMP  RGD 
Rac1Ratc-Jun N-terminal kinases MAPK signaling pathway   ISORAC1 (Homo sapiens) RGD 
Rac1Mousec-Jun N-terminal kinases MAPK signaling pathway   ISORAC1 (Homo sapiens) RGD 
MAP3K1Humanthe extracellular signal-regulated Raf/Mek/Erk signaling pathway   IMP  RGD 
Map3k1Ratthe extracellular signal-regulated Raf/Mek/Erk signaling pathway   ISOMAP3K1 (Homo sapiens) RGD 
Map3k1Mousethe extracellular signal-regulated Raf/Mek/Erk signaling pathway   ISOMAP3K1 (Homo sapiens) RGD 
Objects Annotated

Genes (Rattus norvegicus)
Cdc42  (cell division cycle 42)
Map3k1  (mitogen-activated protein kinase kinase kinase 1)
Map3k2  (mitogen activated protein kinase kinase kinase 2)
Map3k3  (mitogen activated protein kinase kinase kinase 3)
Map3k4  (mitogen activated protein kinase kinase kinase 4)
Rac1  (Rac family small GTPase 1)

Genes (Mus musculus)
Cdc42  (cell division cycle 42)
Map3k1  (mitogen-activated protein kinase kinase kinase 1)
Map3k2  (mitogen-activated protein kinase kinase kinase 2)
Map3k3  (mitogen-activated protein kinase kinase kinase 3)
Map3k4  (mitogen-activated protein kinase kinase kinase 4)
Rac1  (Rac family small GTPase 1)

Genes (Homo sapiens)
CDC42  (cell division cycle 42)
MAP3K1  (mitogen-activated protein kinase kinase kinase 1)
MAP3K2  (mitogen-activated protein kinase kinase kinase 2)
MAP3K3  (mitogen-activated protein kinase kinase kinase 3)
MAP3K4  (mitogen-activated protein kinase kinase kinase 4)
RAC1  (Rac family small GTPase 1)


Additional Information