RGD Reference Report - MEK1/2 dual-specificity protein kinases: Structure and regulation. - Rat Genome Database

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MEK1/2 dual-specificity protein kinases: Structure and regulation.

Authors: Roskoski R, JR 
Citation: Roskoski R Jr Biochem Biophys Res Commun. 2012 Jan 6;417(1):5-10. Epub 2011 Dec 8.
RGD ID: 5686410
Pubmed: PMID:22177953   (View Abstract at PubMed)
DOI: DOI:10.1016/j.bbrc.2011.11.145   (Journal Full-text)

MEK1 and MEK2 are related protein kinases that participate in the RAS-RAF-MEK-ERK signal transduction cascade. This cascade participates in the regulation of a large variety of processes including apoptosis, cell cycle progression, cell migration, differentiation, metabolism, and proliferation. Moreover, oncogenic mutations in RAS or B-RAF are responsible for a large proportion of human cancers. MEK1 is activated by phosphorylation of S218 and S222 in its activation segment as catalyzed by RAF kinases in an intricate process that involves a KSR scaffold. Besides functioning as a scaffold, the kinase activity of KSR is also required for MEK activation. MEK1 regulation is unusual in that S212 phosphorylation in its activation segment is inhibitory. Moreover, active ERK catalyzes a feedback inhibitory phosphorylation of MEK1 T292 that serves to downregulate the pathway.



Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations


  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ARAFHumanthe extracellular signal-regulated Raf/Mek/Erk signaling pathway   TAS  RGD 
ArafRatthe extracellular signal-regulated Raf/Mek/Erk signaling pathway   ISOARAF (Homo sapiens) RGD 
ArafMousethe extracellular signal-regulated Raf/Mek/Erk signaling pathway   ISOARAF (Homo sapiens) RGD 
BRAFHumanthe extracellular signal-regulated Raf/Mek/Erk signaling pathway   TAS  RGD 
BrafRatthe extracellular signal-regulated Raf/Mek/Erk signaling pathway   ISOBRAF (Homo sapiens) RGD 
BrafMousethe extracellular signal-regulated Raf/Mek/Erk signaling pathway   ISOBRAF (Homo sapiens) RGD 
HRASHumanthe extracellular signal-regulated Raf/Mek/Erk signaling pathway   TAS  RGD 
HrasRatthe extracellular signal-regulated Raf/Mek/Erk signaling pathway   ISOHRAS (Homo sapiens) RGD 
HrasMousethe extracellular signal-regulated Raf/Mek/Erk signaling pathway   ISOHRAS (Homo sapiens) RGD 
KRASHumanthe extracellular signal-regulated Raf/Mek/Erk signaling pathway   TAS  RGD 
KSR1Humanthe extracellular signal-regulated Raf/Mek/Erk signaling pathway   TAS  RGD 
KSR2Humanthe extracellular signal-regulated Raf/Mek/Erk signaling pathway   TAS  RGD 
KrasRatthe extracellular signal-regulated Raf/Mek/Erk signaling pathway   ISOKRAS (Homo sapiens) RGD 
KrasMousethe extracellular signal-regulated Raf/Mek/Erk signaling pathway   ISOKRAS (Homo sapiens) RGD 
Ksr1Ratthe extracellular signal-regulated Raf/Mek/Erk signaling pathway   ISOKSR1 (Homo sapiens) RGD 
Ksr1Mousethe extracellular signal-regulated Raf/Mek/Erk signaling pathway   ISOKSR1 (Homo sapiens) RGD 
Ksr2Mousethe extracellular signal-regulated Raf/Mek/Erk signaling pathway   ISOKSR2 (Homo sapiens) RGD 
NRASHumanthe extracellular signal-regulated Raf/Mek/Erk signaling pathway   TAS  RGD 
NrasRatthe extracellular signal-regulated Raf/Mek/Erk signaling pathway   ISONRAS (Homo sapiens) RGD 
NrasMousethe extracellular signal-regulated Raf/Mek/Erk signaling pathway   ISONRAS (Homo sapiens) RGD 
RAF1Humanthe extracellular signal-regulated Raf/Mek/Erk signaling pathway   TAS  RGD 
Raf1Ratthe extracellular signal-regulated Raf/Mek/Erk signaling pathway   ISORAF1 (Homo sapiens) RGD 
Raf1Mousethe extracellular signal-regulated Raf/Mek/Erk signaling pathway   ISORAF1 (Homo sapiens) RGD 
Objects Annotated

Genes (Rattus norvegicus)
Araf  (A-Raf proto-oncogene, serine/threonine kinase)
Braf  (B-Raf proto-oncogene, serine/threonine kinase)
Hras  (HRas proto-oncogene, GTPase)
Kras  (KRAS proto-oncogene, GTPase)
Ksr1  (kinase suppressor of ras 1)
Nras  (NRAS proto-oncogene, GTPase)
Raf1  (Raf-1 proto-oncogene, serine/threonine kinase)

Genes (Mus musculus)
Araf  (Araf proto-oncogene, serine/threonine kinase)
Braf  (Braf transforming gene)
Hras  (Harvey rat sarcoma virus oncogene)
Kras  (Kirsten rat sarcoma viral oncogene homolog)
Ksr1  (kinase suppressor of ras 1)
Ksr2  (kinase suppressor of ras 2)
Nras  (neuroblastoma ras oncogene)
Raf1  (v-raf-leukemia viral oncogene 1)

Genes (Homo sapiens)
ARAF  (A-Raf proto-oncogene, serine/threonine kinase)
BRAF  (B-Raf proto-oncogene, serine/threonine kinase)
HRAS  (HRas proto-oncogene, GTPase)
KRAS  (KRAS proto-oncogene, GTPase)
KSR1  (kinase suppressor of ras 1)
KSR2  (kinase suppressor of ras 2)
NRAS  (NRAS proto-oncogene, GTPase)
RAF1  (Raf-1 proto-oncogene, serine/threonine kinase)


Additional Information