Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 2.7.11.25 extracted from

  • 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 (2011), Proc. Natl. Acad. Sci. USA, 108, 17349-17354.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 2.7.11.25

Cloned(Commentary)

Cloned (Comment) Organism
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 Mus musculus

Protein Variants

Protein Variants Comment Organism
additional information generation of RhoA deletions in Map3k1 wild-type, heterozygous, and knockout genetic backgrounds Mus musculus

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Mus musculus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + c-Jun Mus musculus MAP3K1 phosphorylates and activates a JNK-c-Jun module ADP + phosphorylated c-Jun
-
 ?

Organism

Organism UniProt Comment Textmining
Mus musculus P53349
-
-

Source Tissue

Source Tissue Comment Organism Textmining
epithelium
-
 Mus musculus
-
eyelid MAP3K1 is highly expressed in the developing eyelid tip epithelial cells before eyelid closure Mus musculus
-
fetus
-
 Mus musculus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + c-Jun MAP3K1 phosphorylates and activates a JNK-c-Jun module Mus musculus ADP + phosphorylated c-Jun
-
 ?

Synonyms

Synonyms Comment Organism
MAP3K1
-
 Mus musculus
mitogen-activated protein kinase kinase kinase 1
-
 Mus musculus

Cofactor

Cofactor Comment Organism Structure
ATP
-
 Mus musculus

Expression

Organism Comment Expression
Mus musculus RhoA knockout in the ocular surface epithelium decreases MAP3K1 expression down
Mus musculus molecular mechanisms that control MAP3K1 expression, c-Jun regulates the Map3k1 promoter, overview additional information
Mus musculus 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 up

General Information

General Information Comment Organism
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 Mus musculus
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 Mus musculus
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 Mus musculus