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Literature summary extracted from

  • Cuevas, B.D.; Abell, A.N.; Johnson, G.L.
    Role of mitogen-activated protein kinase kinase kinases in signal integration (2007), Oncogene, 26, 3159-3171.
    View publication on PubMed

Activating Compound

EC Number Activating Compound Comment Organism Structure
2.7.11.25 progesterone induces c-Mos expression Xenopus sp.

Application

EC Number Application Comment Organism
2.7.11.25 medicine gene amplification and corresponding increased Tpl-2 expression in some human breast cancers Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
2.7.11.25 additional information MEKK1 knockdown in invasive human breast carcinoma cells leads to reduced uPA expression, cell migration, and invasiveness Homo sapiens
2.7.11.25 additional information MEKK1-4 knockout mice, MEKK3 knockout is embryo-lethal, displaying inadequate fetal-maternal vascularization. MEKK4 knockout is largely perinatal lethal, and associated with defective neural tube closure, shows loss of JNK and p38 activation. MEKK1-2 knockouts are associated with impaired tissue remodeling associated with wound healing and homeostasis, expression of JunB and Fra-2 is markedly increased in MEKK1-deficient mouse fibroblasts. MLK3-deficient mice are viable and fertile with only a mild defect in the epidermal tissue of the dorsal midline. Mouse embryos deficient in either B-Raf or C-Raf die before day E12.5. A-Raf deficient mice die perinatally at 1-3 weeks of age. Tpl2-deficient mice are viable and appear indistinguishable from littermates, produce reduced levels of TNFalpha in response to LPS injection, are resistant to LPS/D-galactosamine-induced pathology. TAK1-deficient mouse embryo fibroblasts show decreased IL-1beta-induced IL-6 expression, TAK1-deficient keratinocytes develop a severe postnatal inflammation, loss of MEKK1 does not alter the course of tumorigenesis or inhibit primary tumor growth, intimal hyperplasia is significantly reduced Mus musculus

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.7.11.25 BAY 43-9006 c-Raf inhibitor, shows promising response rate in patients with primary renal cell carcinomas Homo sapiens
2.7.11.25 CEP-1347 inhibits MLKs and is well tolerated in human trials, does not perform in trials for neurodegenerative disorders such as Parkinson´s disease Homo sapiens

Organism

EC Number Organism UniProt Comment Textmining
2.7.11.25 Homo sapiens
-
-
-
2.7.11.25 Mus musculus
-
-
-
2.7.11.25 Rattus norvegicus
-
-
-
2.7.11.25 Xenopus sp.
-
-
-

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.7.11.25 breast carcinoma cell
-
 Homo sapiens
-
2.7.11.25 carcinoma cell line A-Raf is rarely mutated in human cancers Homo sapiens
-
2.7.11.25 embryo
-
 Mus musculus
-
2.7.11.25 fibroblast constitutive c-Mos expression transforms fibroblasts Mus musculus
-
2.7.11.25 keratinocyte
-
 Mus musculus
-
2.7.11.25 MOLT-4 cell mutated A-Raf Homo sapiens
-
2.7.11.25 oocyte
-
 Xenopus sp.
-
2.7.11.25 renal cell carcinoma cell c-Raf Homo sapiens
-
2.7.11.25 thymoma cell Tpl-2 isolated from Moloney leukemia virus-induced thymoma cells Rattus norvegicus
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.7.11.25 ATP + ERK5
-
 Mus musculus ADP + phosphorylated ERK5
-
 ?
2.7.11.25 additional information MEKK3 is required for IL-1R and LPS-induced IL-6 production in fibroblasts Mus musculus ?
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.7.11.25 A-Raf
-
 Mus musculus
2.7.11.25 B-Raf
-
 Mus musculus
2.7.11.25 c-mos
-
 Mus musculus
2.7.11.25 c-mos
-
 Xenopus sp.
2.7.11.25 C-Raf
-
 Mus musculus
2.7.11.25 C-Raf
-
 Homo sapiens
2.7.11.25 MEKK1
-
 Mus musculus
2.7.11.25 MEKK1
-
 Homo sapiens
2.7.11.25 MEKK2
-
 Mus musculus
2.7.11.25 MEKK2
-
 Homo sapiens
2.7.11.25 MEKK3
-
 Mus musculus
2.7.11.25 MEKK3
-
 Homo sapiens
2.7.11.25 MEKK4
-
 Mus musculus
2.7.11.25 MEKK4
-
 Homo sapiens
2.7.11.25 mitogen-activated protein kinase kinase kinase
-
 Mus musculus
2.7.11.25 mitogen-activated protein kinase kinase kinase
-
 Homo sapiens
2.7.11.25 mitogen-activated protein kinase kinase kinase
-
 Rattus norvegicus
2.7.11.25 mitogen-activated protein kinase kinase kinase
-
 Xenopus sp.
2.7.11.25 MKKK
-
 Mus musculus
2.7.11.25 MKKK
-
 Homo sapiens
2.7.11.25 MKKK
-
 Rattus norvegicus
2.7.11.25 MKKK
-
 Xenopus sp.
2.7.11.25 MKL3
-
 Mus musculus
2.7.11.25 MLK
-
 Homo sapiens
2.7.11.25 TAK1
-
 Mus musculus
2.7.11.25 TPL-2
-
 Mus musculus
2.7.11.25 TPL-2
-
 Homo sapiens
2.7.11.25 TPL-2
-
 Rattus norvegicus