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Information on EC 2.7.11.25 - mitogen-activated protein kinase kinase kinase and Organism(s) Mus musculus and UniProt Accession P53349

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EC Tree
IUBMB Comments
This enzyme phosphorylates and activates its downstream protein kinase, EC 2.7.12.2, mitogen-activated protein kinase kinase (MAPKK) but requires MAPKKKK for activation. Some members of this family can be activated by p21-activated kinases (PAK/STE20) or Ras. While c-Raf and c-Mos activate the classical MAPK/ERK pathway, MEKK1 and MEKK2 preferentially activate the c-Jun N-terminal protein kinase(JNK)/stress-activated protein kinase (SAPK) pathway . Mitogen-activated protein kinase (MAPK) signal transduction pathways are among the most widespread mechanisms of cellular regulation. Mammalian MAPK pathways can be recruited by a wide variety of stimuli including hormones (e.g. insulin and growth hormone), mitogens (e.g. epidermal growth factor and platelet-derived growth factor), vasoactive peptides (e.g. angiotensin-II and endothelin), inflammatory cytokines of the tumour necrosis factor (TNF) family and environmental stresses such as osmotic shock, ionizing radiation and ischaemic injury.
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Mus musculus
UNIPROT: P53349
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Word Map
The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
+
a [protein]-(L-serine/L-threonine)
=
+
a [protein]-(L-serine/L-threonine) phosphate
Synonyms
b-raf, c-raf, mekk1, c-mos, apoptosis signal-regulating kinase 1, mixed lineage kinase, ste11, mekk3, map3k1, mapkkk, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
(JNK)/stress-activated protein kinase-associated protein 1
-
Jun N-terminal protein kinase
-
mitogen-activated protein kinase kinase kinase 1
-
apoptosis signal-regulating kinase
-
-
apoptosis signal-regulating kinase 1
apoptosis signal-regulating kinase 2
-
c-mos
D-MEKK1
-
-
Dual leucine zipper bearing kinase
GCKR
-
-
germinal center kinase-related enzyme
-
-
HsNIK
-
-
-
-
Leucine-zipper protein kinase
-
-
-
-
MAP 3-kinase
-
-
MAP kinase kinase kinase
-
-
MAP/ERK kinase kinase 1
-
-
MAP3K
MAP3K1
-
-
MAP3K6
-
-
MAPK-upstream kinase
-
-
-
-
MAPK/ERKkinase kinase 3
-
-
MEK kinase 1
-
-
MEK kinase 3
-
-
MEKK3
MEKK5
-
-
MEKK8
-
-
mitogen-activated protein kinase kinase kinase
mitogen-activated protein kinase kinase kinase 1
-
-
mitogen-activated protein kinase kinase kinase 4
-
mitogen-activated protein kinase kinase kinase kinase
-
-
mitogen-activated protein/ERK kinase kinase 3
-
-
Mixed Lineage Kinase
-
five characterized forms
MKKK
-
-
MKL3
-
-
MLK
-
five characterized forms termed MLK1, 2, 3, 4 or 7
MLK1
-
-
MLK2
-
-
MLK3
-
-
MLK4
-
-
NF-kappa beta-inducing kinase
-
-
-
-
Serine/threonine protein kinase NIK
-
-
-
-
TAK1 (three isoforms termed A,B and C)
-
-
TAO kinase
-
three different forms
TAO1-2
-
-
TGF-beta-activated kinase-1
-
TGFalpha activated kinase
-
-
TGFbeta activated kinase 1
-
-
Thousand And One kinase
-
-
Tlp2
-
-
transforming growth factor beta-activated kinase 1
-
-
tumor progression locus-2
-
-
tumour progression locus 2
-
-
additional information
-
MEKK2 and MEKK3 belong to the MEKK/Ste11 subfamily of the MAP3K family of enzymes
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + a [protein]-(L-serine/L-threonine) = ADP + a [protein]-(L-serine/L-threonine) phosphate
show the reaction diagram
molecular mechanism of MEKK2 and MEKK3
-
SYSTEMATIC NAME
IUBMB Comments
ATP:protein phosphotransferase (MAPKKKK-activated)
This enzyme phosphorylates and activates its downstream protein kinase, EC 2.7.12.2, mitogen-activated protein kinase kinase (MAPKK) but requires MAPKKKK for activation. Some members of this family can be activated by p21-activated kinases (PAK/STE20) or Ras. While c-Raf and c-Mos activate the classical MAPK/ERK pathway, MEKK1 and MEKK2 preferentially activate the c-Jun N-terminal protein kinase(JNK)/stress-activated protein kinase (SAPK) pathway [2]. Mitogen-activated protein kinase (MAPK) signal transduction pathways are among the most widespread mechanisms of cellular regulation. Mammalian MAPK pathways can be recruited by a wide variety of stimuli including hormones (e.g. insulin and growth hormone), mitogens (e.g. epidermal growth factor and platelet-derived growth factor), vasoactive peptides (e.g. angiotensin-II and endothelin), inflammatory cytokines of the tumour necrosis factor (TNF) family and environmental stresses such as osmotic shock, ionizing radiation and ischaemic injury.
CAS REGISTRY NUMBER
COMMENTARY hide
146702-84-3
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + c-Jun
ADP + phosphorylated c-Jun
show the reaction diagram
MAP3K1 phosphorylates and activates a JNK-c-Jun module
-
-
?
ATP + protein
ADP + phosphoprotein
show the reaction diagram
JSAP1 functions as a scaffold protein in the JNK3 cascade
-
-
?
ATP + ASK1
ADP + phosphorylated ASK1
show the reaction diagram
ASK2 activates ASK1 by direct phosphorylation
-
-
?
ATP + ERK
ADP + phosphorylated ERK
show the reaction diagram
ATP + ERK5
ADP + phosphorylated ERK5
show the reaction diagram
-
-
-
-
?
ATP + GSK3beta
ADP + phosphorylated GSK3beta
show the reaction diagram
-
regulates phosphorylation at serine 9
-
-
?
ATP + JNK
ADP + phosphorylated JNK
show the reaction diagram
ATP + MEK
ADP + phosphorylated MEK
show the reaction diagram
ATP + MEK1
ADP + phosphorylated MEK1
show the reaction diagram
ATP + MEK5
ADP + phosphorylated MEK5
show the reaction diagram
ATP + MKK
ADP + phosphorylated MKK
show the reaction diagram
ATP + MKK1
ADP + phosphorylated MKK1
show the reaction diagram
ATP + MKK3
ADP + phosphorylated MKK3
show the reaction diagram
ATP + MKK4
ADP + phosphorylated MKK4
show the reaction diagram
ATP + MKK6
ADP + phosphorylated MKK6
show the reaction diagram
ATP + MKK7
ADP + phosphorylated MKK7
show the reaction diagram
ATP + p38
ADP + phosphorylated p38
show the reaction diagram
-
ASK1, TAK1
-
-
?
ATP + protein
ADP + phosphoprotein
show the reaction diagram
selectively regulates the c-Jun amino terminal kinase pathway
-
-
?
ATP + Ror2
ADP + phospho-Ror2
show the reaction diagram
BAD + ATP
BAD-phosphate + ADP
show the reaction diagram
-
activation of the proapoptotic protein BAD
-
-
?
MAP2K + ATP
MAP2K-phosphate + ADP
show the reaction diagram
-
involved in reducing c-jun N-terminal kinase (JNK, MAPK8) activation and protecting the mice from nickel-induced acute lung injury
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + c-Jun
ADP + phosphorylated c-Jun
show the reaction diagram
MAP3K1 phosphorylates and activates a JNK-c-Jun module
-
-
?
ATP + protein
ADP + phosphoprotein
show the reaction diagram
JSAP1 functions as a scaffold protein in the JNK3 cascade
-
-
?
ATP + ERK
ADP + phosphorylated ERK
show the reaction diagram
-
PI3K/PKC/Raf-1-independent activation of the MEK/ERK signaling pathway
-
-
?
ATP + MEK
ADP + phosphorylated MEK
show the reaction diagram
-
PI3K/PKC/Raf-1-independent activation of the MEK/ERK signaling pathway
-
-
?
ATP + MEK1
ADP + phosphorylated MEK1
show the reaction diagram
-
MEK1 activates the ERK2 signaling pathway
-
-
?
ATP + MEK5
ADP + phosphorylated MEK5
show the reaction diagram
-
activated MEK5 activates ERK5
-
-
?
ATP + MKK
ADP + phosphorylated MKK
show the reaction diagram
-
induction of the JNK pathway activation
-
-
?
ATP + MKK1
ADP + phosphorylated MKK1
show the reaction diagram
-
MKK1 activates the ERK2 signaling pathway
-
-
?
ATP + MKK3
ADP + phosphorylated MKK3
show the reaction diagram
-
activation of the p38 MAP kinase signaling pathway leading to apoptosis
-
-
?
ATP + MKK4
ADP + phosphorylated MKK4
show the reaction diagram
ATP + MKK6
ADP + phosphorylated MKK6
show the reaction diagram
-
activation of the p38 MAP kinase signaling pathway leading to apoptosis
-
-
?
ATP + MKK7
ADP + phosphorylated MKK7
show the reaction diagram
-
activation of the Jun N-terminal kinase, JNK, signaling pathway leading to apoptosis
-
-
?
ATP + protein
ADP + phosphoprotein
show the reaction diagram
selectively regulates the c-Jun amino terminal kinase pathway
-
-
?
ATP + Ror2
ADP + phospho-Ror2
show the reaction diagram
TGF-beta activated kinase 1, a MAPKKK, interacts with Ror2 and phosphorylates its intracellular carboxyterminal serine/thronine/proline-rich, STP, domain, Wnt-ligand binding differentially controls the Ror2/TAK1 interaction, Ror2 seems to act as a Wnt co-receptor enhancing Wnt-dependent canonical pathways while Tyr- and Ser/Thr-phosphorylation of Ror2 negatively controls the efficiency of these pathways, overview
-
-
?
BAD + ATP
BAD-phosphate + ADP
show the reaction diagram
-
activation of the proapoptotic protein BAD
-
-
?
MAP2K + ATP
MAP2K-phosphate + ADP
show the reaction diagram
-
involved in reducing c-jun N-terminal kinase (JNK, MAPK8) activation and protecting the mice from nickel-induced acute lung injury
-
-
?
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mg2+
required
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
p105
-
blocks the ability of TPL-2 to interact with and phosphorylate MEk
-
p38
-
negatively regulates tAK1 activation
-
PD98059
-
-
RNAi
-
knockdown of TAK1 impairs p38 and JNK activation by IL-1 and TNF
-
shRNA
-
silences GCKR expression
-
siRNA
transfection of siRNA for ASK1 into cells reduces expression of not only ASK1 but also ASK2
-
thioredoxin
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
CpG
-
ASK1, TAK1, MEKK3
H2O2
-
ASK1
interleukin 1
-
TPL-2, TAK1, MEKK1 and MEKK3
-
lipopolysaccharide
-
ASK1, TPL-2, TAK1, MEKK1 and MEKK3
methylglyoxal
-
induces the PI3K/PKC/Raf-1-independent MEK/ERK signaling pathway by activation of MEKK1, accumulates in case of diabetes
protein CD40
-
TPL-2
-
protein PGN
-
ASK1
-
protein pI:C
-
ASK1
-
protein TAB1
-
positively regulates TAK1 activity
-
protein TAB2
-
positively regulates TAK1 activity
-
protein TNF
-
ASK1, TPL-2, MLK3, TAK1, MEKK1 and MEKK3
-
reactive oxygene species
-
the enzyme is oxidative stress-induced
-
sorbitol
-
induces phosphorylation of Ser526, response to osmotic stress
TNF-alpha
-
treatment with TNF-alpha dissociates the inhibitor thioredoxin from the enzyme's N-terminus
-
Wnt3a
-
induces GCKR kinase activity. APC, Asef, and Rac are required for Wnt signaling to activate GCKR
-
additional information
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.4
-
assay at
7.5
-
assay at
7.6
-
assay at
7.9
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
-
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
MAP3K1 is highly expressed in the developing eyelid tip epithelial cells before eyelid closure
Manually annotated by BRENDA team
-
TPL-2, TAK1
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
-
highly expressed
Manually annotated by BRENDA team
-
TPL-2 and MEKK1
Manually annotated by BRENDA team
the enzyme is most abundantly expressed in developing nervous tissues
Manually annotated by BRENDA team
-
highly expressed
Manually annotated by BRENDA team
-
highly expressed
Manually annotated by BRENDA team
-
overxpressed
Manually annotated by BRENDA team
-
highly expressed
Manually annotated by BRENDA team
-
TAK1
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
to a lesser degree
Manually annotated by BRENDA team
additional information
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
decreased MAP3K1 expression causes delayed eyelid closure in Map3k1 hemizygotes. MAP3K1 inactivation reduces AP-1 activity and PAI-1 expression both in cells and developing eyelids
metabolism
mitogen-activated protein kinase kinase kinase 1 (MAP3K1) forms with c-Jun a regulatory axis that orchestrates morphogenesis by integrating two different networks of eyelid closure signals. TGF-alpha/EGFR-RhoA module initiates one of these networks by inducing c-Jun expression which, in a phosphorylation-independent manner, binds to the Map3k1 promoter and causes an increase in MAP3K1 expression. RhoA knockout in the ocular surface epithelium disturbs this network by decreasing MAP3K1 expression, and causes delayed eyelid closure in Map3k1 hemizygotes. The second network is initiated by the enzymatic activity of MAP3K1, which phosphorylates and activates a JNK-c-Jun module, leading to AP-1 transactivation and induction of its downstream genes, such as Pai-1
physiological function
MAP3K1 is the nexus of an intracrine regulatory loop connecting the TGF-alpha/EGFR/RhoA-c-Jun and JNK-c-Jun-AP-1 pathways in developmental eyelid closure. the kinase activity of MAP3K1 is required for activation of the JNK-c-Jun pathway, induction of AP-1 activity, and PAI-1 expression during eyelid development. RhoA is an accessory to MAP3K1 signaling
evolution
the enzyme is a member of the MLK family
malfunction
mice deficient in ZPK have twice as many spinal motoneurons as do their wild-type littermates. Nuclear HB9/MNX1-positive motoneuron pools are generated similarly in the spinal cord of both ZPK/DLK-deficient and wild-type embryos. Significantly less apoptotic motoneurons are found in ZPK/DLK-deficient embryos compared to wild-type embryos, resulting in retention of excess numbers of motoneurons after birth. The excess motoneurons remain viable without atrophic changes in the ZPK/DLK-deficient mice surviving into adulthood. Analysis of the diaphragm and the phrenic nerve reveals that clustering and innervation of neuromuscular junctions are indistinguishable between ZPK/DLK-deficient and wild-type mice, whereas the proximal portion of the phrenic nerve of ZPK/DLK-deficient mice contain significantly more axons than the distal portion. Some excess ZPK/DLK-deficient motoneurons survive without atrophy despite failure to establish axonal contact with their targets
physiological function
activation of mitogen-activated protein kinase pathways is critically involved in naturally occurring programmed cell death of motoneurons during development. Enzyme ZPK, also called DLK, (ZPK/DLK), a mitogen-activated protein kinase kinase kinase, is a critical mediator of programmed cell death of motoneurons. The enzyme has a distinctive role in neural development and in naturally occurring programmed cell death
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
M3K1_MOUSE
1493
0
161289
Swiss-Prot
other Location (Reliability: 4)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
-
dimerization through the catalytic domain is essential for MEKK2 activation, the dimerization motif is in the catalytic domain, the N-terminal domain is not required for dimerization, overview
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
proteolytic modification
-
cleavage by caspase-3 at a specific C-terminal cleavage site generates a 91 kDa, catalytically active enzyme fragment
additional information
-
the active MEKK1 stimulates its own ubiquitinylation in vivo which has a negatively regulating function
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C433A
-
completely abolishes its interaction with RhoA
C441A
-
site-directed mutagenesis, the mutant enzyme is not ubiquitinylated and thus shows a higher ERK activating activity
F1443A
F571A
-
site-directed mutagenesis of MEKK2, inactive mutant
G452C/R454C/N455D
-
completely abolishes its interaction with RhoA
I1394/L1402A
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
I1445A
-
site-directed mutagenesis of MEKK1, the mutation has a deleterious effect on MEKK1 function
I1454A
-
site-directed mutagenesis of MEKK1, the mutation abolishes the in vitro interaction with MKK4, but retains the in vivo activity
I573A
-
site-directed mutagenesis of MEKK2, inactive mutant
K1361R
-
shows remarkable increase in the number of neural tube defects
L1402A/F1443A
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
L1458A
-
site-directed mutagenesis of MEKK1, the mutation has a deleterious effect on MEKK1 function
L582A/P583A
-
site-directed mutagenesis of MEKK2, inactive mutant
P1452A
-
site-directed mutagenesis of MEKK1, the mutation has a deleterious effect on MEKK1 function
P1455A
-
site-directed mutagenesis of MEKK1, the mutation has a deleterious effect on MEKK1 function
P580A
-
site-directed mutagenesis of MEKK2, the mutant shows 82% of wild-type activity
P584A
-
site-directed mutagenesis of MEKK2, the mutant shows activity similar to the wild-type enzyme
Q1405R/Q1406R
-
site-directed mutagenesis C-terminal to the subdomain VIII, creation of an optimal recognition site for protease furin, the mutant binds MKK4 more tightly than the wild-type enzyme, MKK4 binding protects the mutant enzyme from proteolytic cleavage
S1459A
-
site-directed mutagenesis of MEKK1, the mutation abolishes the in vitro interaction with MKK4, but retains the in vivo activity
S519A
-
site-directed mutagenesis, MEKK2 phosphorylation site mutant, inactive mutant
S526A
-
site-directed mutagenesis, MEKK3 phosphorylation site mutant, inactive mutant
S526A/K391M
-
critical phosphorylation site and catalytic site
T521A
-
site-directed mutagenesis, MEKK2 phosphorylation site mutant, the mutant shows slightly reduced activity compared to the wild-type enzyme
T523A
-
site-directed mutagenesis, MEKK2 phosphorylation site mutant, the mutant shows slightly reduced activity compared to the wild-type enzyme
T575A/Q576A/P577A
-
site-directed mutagenesis of MEKK2, inactive mutant
V586A
-
site-directed mutagenesis of MEKK2, the mutant shows activity similar to the wild-type enzyme
additional information
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant protein by tandem affinity purification
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
HEK293 cells are transfected with pMap3k1-luc together with the expression vectors for active RhoA, dominant-negative RhoA, and ROCKII and treated with TGF-alpha, inhibition of histone deacetylase with sodium butyrate or trichostatin A increases luciferase expression in pMap3k1-luc transfected HEK293 cells. Molecular mechanism of Map3k1 promoter regulation, overview
expressed as native and mutant FLAG-tag/HA-tag fusion protein in HEK293T cells, coexpression expreiments with TAK1
-
expressed together with or without MEKK3 in HEK293T cells
-
expression of a MEKK1 promoter-driven beta-Gal fusion protein in Mekk1deltaKD/deltaKD mice
-
expression of GST-tagged full length MEKK2 and MEKK2 C-terminal and N-terminal fragments, i.e. of residues 1-619, 342-619, and 342-424, in COS-1 cells
-
expression of HA-tagged active MEKK2 and inactive S519A MEKK2 mutant catalytic sites, expression of wild-type and mutant full length MEKK2s and of wild-type and mutant MEKK3s
-
expression of His6-tagged MEKK1 subdomain VIII, comprising residues 1174-1493, His6-tagged wild-type, full-length enzyme, and His6-tagged mutant enzymes F1443A, I1394/L1402A, Q1405R/Q1406R, and L1402A/F1443A in HeLa and COS-1 cells
-
full-length ASK2 cDNA inserted in pJG4-5, kinase-negative mutant of ASK1 inserted in pEG202. ASK1 and ASK2 constructs co-transformed along with the reporter plasmid pSH18-34 in EGY48 yeast strains, mutants transfected into HEK293 cells and MEF cells
into pBluescript, SF-9 insect cells infected with baculovirus expressing either MEKK4 or the kinase inactive form of MEKK4
-
into PCR3.1 vector and expressed in HEK-293 cells
-
MEKK1 fragments (1-132, 149-347, 149-636, 630-772, 766-1173, 766-1493, 1-719, and 565-1174) incorporated into pAS1CYH2 vector, expressed in Saccharomyces cerevisiae Y190 cells
-
MEKK2, DNA and amino acid sequence determination, expression of wild-type and mutant MEKK2 by reticulocyte lysate TnT T7 mixture, expression of wild-type and mutant MEKK2 and MEKK1 in COS-1 cells and in HeLa cells, coexpression with ERK5 in COS-1 cells
-
TAK1 expressed in HeLa cells
-
TAK1 expression in HEK-293 cells, Ror2-Tak1 interaction analysis by expression in the yeast two-hybrid system
transient co-expression of MEKK1 and FAK in HEK293 cells
-
wild-type and mutant enzyme
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
c-Jun expression binds in a phosphorylation-independent manner to the Map3k1 promoter and causes an increase in MAP3K1 expression. Activation of the EGF receptor leads to MAP3K1 induction. Inhibition of histone deacetylase with sodium butyrate or trichostatin A increases luciferase expression in pMap3k1-luc transfected HEK293 cells
molecular mechanisms that control MAP3K1 expression, c-Jun regulates the Map3k1 promoter, overview
RhoA knockout in the ocular surface epithelium decreases MAP3K1 expression
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
additional information
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Ito, M.; Yoshioka, K.; Akechi, M.; Yamashita, S.; Takamatsu, N.; Sugiyama, K.; Hibi, M.; Nakabeppu, Y.; Shiba, T.; Yamamoto, K.I.
JSAP1, a novel jun N-terminal protein kinase (JNK)-binding protein that functions as a Scaffold factor in the JNK signaling pathway
Mol. Cell. Biol.
19
7539-7548
1999
Mus musculus (P53349), Mus musculus
Manually annotated by BRENDA team
Gerwins, P.; Blank, J.L.; Johnson, G.L.
Cloning of a novel mitogen-activated protein kinase kinase kinase, MEKK4, that selectively regulates the c-Jun amino terminal kinase pathway
J. Biol. Chem.
272
8288-8295
1997
Mus musculus (O08648), Mus musculus
Manually annotated by BRENDA team
Schweifer, N.; Valk, P.J.; Delwel, R.; Cox, R.; Francis, F.; Meier-Ewert, S.; Lehrach, H.; Barlow, D.P.
Characterization of the C3 YAC contig from proximal mouse chromosome 17 and analysis of allelic expression of genes flanking the imprinted Igf2r gene
Genomics
43
285-297
1997
Mus musculus (O08648)
Manually annotated by BRENDA team
Lange-Carter, C.A.; Pleiman, C.M.; Gardner, A.M.; Blumer, K.J.; Johnson, G.L.
A divergence in the MAP kinase regulatory network defined by MEK kinase and Raf
Science
260
315-319
1993
Mus musculus (P53349), Mus musculus
Manually annotated by BRENDA team
Huang, J.; Tu, Z.; Lee, F.S.
Mutations in protein kinase subdomain X differentially affect MEKK2 and MEKK1 activity
Biochem. Biophys. Res. Commun.
303
532-540
2003
Mus musculus
Manually annotated by BRENDA team
Takeda, K.; Matsuzawa, A.; Nishitoh, H.; Ichijo, H.
Roles of MAPKKK ASK1 in stress-induced cell death
Cell Struct. Funct.
28
23-29
2003
Caenorhabditis elegans, Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Cuevas, B.D.; Abell, A.N.; Witowsky, J.A.; Yujiri, T.; Johnson, N.L.; Kesavan, K.; Ware, M.; Jones, P.L.; Weed, S.A.; DeBiasi, R.L.; Oka, Y.; Tyler, K.L.; Johnson, G.L.
MEKK1 regulates calpain-dependent proteolysis of focal adhesion proteins for rear-end detachment of migrating fibroblasts
EMBO J.
22
3346-3355
2003
Mus musculus
Manually annotated by BRENDA team
Zhang, D.; Facchinetti, V.; Wang, X.; Huang, Q.; Qin, J.; Su, B.
Identification of MEKK2/3 serine phosphorylation site targeted by the Toll-like receptor and stress pathways
EMBO J.
25
97-107
2006
Mus musculus
Manually annotated by BRENDA team
Witowsky, J.A.; Johnson, G.L.
Ubiquitylation of MEKK1 inhibits its phosphorylation of MKK1 and MKK4 and activation of the ERK1/2 and JNK pathways
J. Biol. Chem.
278
1403-1406
2003
Mus musculus
Manually annotated by BRENDA team
Tu, Z.; Lee, F.S.
Subdomain VIII is a specificity-determining region in MEKK1
J. Biol. Chem.
278
48498-48505
2003
Mus musculus
Manually annotated by BRENDA team
Cheng, J.; Yu, L.; Zhang, D.; Huang, Q.; Spencer, D.; Su, B.
Dimerization through the catalytic domain is essential for MEKK2 activation
J. Biol. Chem.
280
13477-13482
2005
Mus musculus
Manually annotated by BRENDA team
Fritz, A.; Brayer, K.J.; McCormick, N.; Adams, D.G.; Wadzinski, B.E.; Vaillancourt, R.R.
Phosphorylation of serine 526 is required for MEKK3 activity and association with 14-3-3 blocks dephosphorylation
J. Biol. Chem.
281
6236-6245
2006
Homo sapiens, Mus musculus, synthetic construct
Manually annotated by BRENDA team
Du, J.; Cai, S.; Suzuki, H.; Akhand, A.A.; Ma, X.; Takagi, Y.; Miyata, T.; Nakashima, I.; Nagase, F.
Involvement of MEKK1/ERK/p21Waf1/Cip1 signal transduction pathway in inhibition of IGF-I-mediated cell growth response by methylglyoxal
J. Cell. Biochem.
88
1235-1246
2003
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Stevens, M.V.; Parker, P.; Vaillancourt, R.R.; Camenisch, T.D.
MEKK4 regulates developmental EMT in the embryonic heart
Dev. Dyn.
235
2761-2770
2006
Mus musculus
Manually annotated by BRENDA team
Takeda, K.; Shimozono, R.; Noguchi, T.; Umeda, T.; Morimoto, Y.; Naguro, I.; Tobiume, K.; Saitoh, M.; Matsuzawa, A.; Ichijo, H.
Apoptosis signal-regulating kinase (ASK) 2 functions as a mitogen-activated protein kinase kinase kinase in a heteromeric complex with ASK1
J. Biol. Chem.
282
7522-7531
2007
Homo sapiens (O95382), Mus musculus (Q9WTR2)
Manually annotated by BRENDA team
Bettinger, B.T.; Amberg, D.C.
The MEK kinases MEKK4/Ssk2p facilitate complexity in the stress signaling responses of diverse systems
J. Cell. Biochem.
101
34-43
2007
Saccharomyces cerevisiae, Drosophila melanogaster, Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Chen, Z.; Cobb, M.H.
Activation of MEKK1 by Rho GTPases
Methods Enzymol.
406
468-478
2006
Homo sapiens, Mus musculus, synthetic construct
Manually annotated by BRENDA team
Deng, M.; Chen, W.L.; Takatori, A.; Peng, Z.; Zhang, L.; Mongan, M.; Parthasarathy, R.; Sartor, M.; Miller, M.; Yang, J.; Su, B.; Kao, W.W.; Xia, Y.
A role for the mitogen-activated protein kinase kinase kinase 1 in epithelial wound healing
Mol. Biol. Cell
17
3446-3455
2006
Mus musculus
Manually annotated by BRENDA team
Shi, C.S.; Huang, N.N.; Harrison, K.; Han, S.B.; Kehrl, J.H.
The mitogen-activated protein kinase kinase kinase kinase GCKR positively regulates canonical and noncanonical Wnt signaling in B lymphocytes
Mol. Cell. Biol.
26
6511-6521
2006
Homo sapiens, Mus musculus, Mus musculus C57BL/6
Manually annotated by BRENDA team
Cuevas, B.D.; Abell, A.N.; Johnson, G.L.
Role of mitogen-activated protein kinase kinase kinases in signal integration
Oncogene
26
3159-3171
2007
Homo sapiens, Mus musculus, Rattus norvegicus, Xenopus sp.
Manually annotated by BRENDA team
Symons, A.; Beinke, S.; Ley, S.C.
MAP kinase kinase kinases and innate immunity
Trends Immunol.
27
40-48
2006
Drosophila melanogaster, Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Winkel, A.; Stricker, S.; Tylzanowski, P.; Seiffart, V.; Mundlos, S.; Gross, G.; Hoffmann, A.
Wnt-ligand-dependent interaction of TAK1 (TGF-beta-activated kinase-1) with the receptor tyrosine kinase Ror2 modulates canonical Wnt-signalling
Cell. Signal.
20
2134-2144
2008
Mus musculus (Q62073)
Manually annotated by BRENDA team
Di, Y.; Li, S.; Wang, L.; Zhang, Y.; Dorf, M.E.
Homeostatic interactions between MEKK3 and TAK1 involved in NF-kappaB signaling
Cell. Signal.
20
705-713
2008
Mus musculus
Manually annotated by BRENDA team
Craig, E.A.; Stevens, M.V.; Vaillancourt, R.R.; Camenisch, T.D.
MAP3Ks as central regulators of cell fate during development
Dev. Dyn.
237
3102-3114
2008
Mus musculus
Manually annotated by BRENDA team
Mongan, M.; Tan, Z.; Chen, L.; Peng, Z.; Dietsch, M.; Su, B.; Leikauf, G.; Xia, Y.
Mitogen-activated protein kinase kinase kinase 1 protects against nickel-induced acute lung injury
Toxicol. Sci.
104
405-411
2008
Mus musculus
Manually annotated by BRENDA team
Itoh, A.; Horiuchi, M.; Wakayama, K.; Xu, J.; Bannerman, P.; Pleasure, D.; Itoh, T.
ZPK/DLK, a mitogen-activated protein kinase kinase kinase, is a critical mediator of programmed cell death of motoneurons
J. Neurosci.
31
7223-7228
2011
Mus musculus (Q60700)
Manually annotated by BRENDA team
Geh, E.; Meng, Q.; Mongan, M.; Wang, J.; Takatori, A.; Zheng, Y.; Puga, A.; Lang, R.A.; Xia, Y.
Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) integrates developmental signals for eyelid closure
Proc. Natl. Acad. Sci. USA
108
17349-17354
2011
Mus musculus (P53349)
Manually annotated by BRENDA team