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Literature summary extracted from

  • Bettinger, B.T.; Amberg, D.C.
    The MEK kinases MEKK4/Ssk2p facilitate complexity in the stress signaling responses of diverse systems (2007), J. Cell. Biochem., 101, 34-43.
    View publication on PubMed

Activating Compound

EC Number Activating Compound Comment Organism Structure
2.7.11.25 Gadd45alpha causes an increase in the activation of both the p38 and JNK pathways, but not the ERK pathway, upregulates MEKK4’s kinase activity to a lesser degree as compared to Gadd45beta or Gadd45gamma Homo sapiens
2.7.11.25 Gadd45beta causes an increase in the activation of both the p38 and JNK pathways, but not the ERK pathway Homo sapiens
2.7.11.25 Gadd45gamma causes an increase in the activation of both the p38 and JNK pathways, but not the ERK pathway Homo sapiens
2.7.11.25 additional information Ssk1p binds and activates the MEKK kinases Ssk2p and Ssk22p, de-phosphorylated Ssk1p binds to the N-terminal auto-inhibitory domain of Ssk2p and Ssk22p, activating their auto-phosphorylation on a conserved threonine residue Saccharomyces cerevisiae

Application

EC Number Application Comment Organism
2.7.11.25 additional information Ssk2p is one of the three MEKK kinases in the HOG pathway, the other two being Ste11p and Ssk22p, Ssk2p is homologous to MEKK4, monitors the integrity of the actin cytoskeleton and regulates its recovery from osmotic stress Saccharomyces cerevisiae
2.7.11.25 additional information two isoforms of MEKK4, monitors the integrity of the actin cytoskeleton and regulates its recovery from osmotic stress, MEKK4 and TRAF4 are involved in the process of neurulation Homo sapiens
2.7.11.25 additional information two isoforms of MEKK4, play a role in downregulating apoptosis during neurulation via the p38 MAPK pathway Mus musculus

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.7.11.25 expressed in COS-7 cells and in yeast Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
2.7.11.25 K1361R shows remarkable increase in the number of neural tube defects Mus musculus
2.7.11.25 additional information deletion of the CRIB domain of MEKK4 diminishes but does not abolish Cdc42 binding Homo sapiens
2.7.11.25 additional information MEKK4-/- mice, protein is not essential for embryonic survival, but more than 80% of mice exhibit neural tube defects and die shortly after birth. Reduced level of IFN-gamma production in response to cytokine treatment. MEKK4-3R mutant, completely abolishes CIN85 interaction and is defective in activating the p38 pathway. Intermediate MKK6 causes reduction in p38 activation in response to both oxidative stress and epidermal growth factor stimulation, less prone to ubiquitination Mus musculus
2.7.11.25 additional information ssk2delta/ssk22delta/ste11delta strain, complementation of the osmo-sensitive phenotype, deletion of the LD domain of Ssk2p results in a serious localization defect when yeast cells are exposed to osmotic stress as well as an inability to facilitate the actin specific functions of Ssk2p Saccharomyces cerevisiae

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.7.11.25 additional information inhibitory function within the N-terminal domain Homo sapiens
2.7.11.25 additional information inhibitory function within the N-terminal domain Saccharomyces cerevisiae

Organism

EC Number Organism UniProt Comment Textmining
2.7.11.25 Drosophila melanogaster
-
-
-
2.7.11.25 Homo sapiens
-
-
-
2.7.11.25 Mus musculus
-
-
-
2.7.11.25 Saccharomyces cerevisiae
-
-
-

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.7.11.25 fibroblast
-
 Mus musculus
-
2.7.11.25 keratinocyte
-
 Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.7.11.25 ATP + cdc42
-
 Homo sapiens ADP + phosphorylated cdc42
-
 ?
2.7.11.25 ATP + MKK3
-
 Drosophila melanogaster ADP + phosphorylated MKK3
-
 ?
2.7.11.25 ATP + MKK3
-
 Mus musculus ADP + phosphorylated MKK3
-
 ?
2.7.11.25 ATP + MKK3
-
 Homo sapiens ADP + phosphorylated MKK3
-
 ?
2.7.11.25 ATP + MKK4
-
 Drosophila melanogaster ADP + phosphorylated MKK4
-
 ?
2.7.11.25 ATP + MKK4
-
 Mus musculus ADP + phosphorylated MKK4
-
 ?
2.7.11.25 ATP + MKK4
-
 Homo sapiens ADP + phosphorylated MKK4
-
 ?
2.7.11.25 ATP + MKK6
-
 Drosophila melanogaster ADP + phosphorylated MKK6
-
 ?
2.7.11.25 ATP + MKK6
-
 Mus musculus ADP + phosphorylated MKK6
-
 ?
2.7.11.25 ATP + MKK6
-
 Homo sapiens ADP + phosphorylated MKK6
-
 ?
2.7.11.25 ATP + Pbs2p
-
 Saccharomyces cerevisiae ADP + phosphorylated Pbs2p
-
 ?
2.7.11.25 ATP + Rac
-
 Homo sapiens ADP + phosphorylated Rac
-
 ?
2.7.11.25 additional information MEKK4 is a signaling protein of the p38 MAPK pathway Drosophila melanogaster ?
-
 ?
2.7.11.25 additional information MEKK4 is a signaling protein of the p38 MAPK pathway Mus musculus ?
-
 ?
2.7.11.25 additional information MEKK4 is a signaling protein of the p38 MAPK pathway Homo sapiens ?
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.7.11.25 D-MEKK1
-
 Drosophila melanogaster
2.7.11.25 D-MEKK1
-
 Mus musculus
2.7.11.25 MAP kinase kinase kinase
-
 Drosophila melanogaster
2.7.11.25 MAP kinase kinase kinase
-
 Mus musculus
2.7.11.25 MAP kinase kinase kinase
-
 Homo sapiens
2.7.11.25 MAP kinase kinase kinase
-
 Saccharomyces cerevisiae
2.7.11.25 MAPKKK
-
 Drosophila melanogaster
2.7.11.25 MAPKKK
-
 Mus musculus
2.7.11.25 MAPKKK
-
 Homo sapiens
2.7.11.25 MAPKKK
-
 Saccharomyces cerevisiae
2.7.11.25 MEKK4
-
 Homo sapiens
2.7.11.25 Ssk22p
-
 Saccharomyces cerevisiae
2.7.11.25 Ssk2p
-
 Saccharomyces cerevisiae
2.7.11.25 Ste11p
-
 Saccharomyces cerevisiae