Activation of the JNK pathway by distantly related protein kinases, MEKK and MUK
1996 (English)In: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 12, no 3, 641-650 p.Article in journal (Refereed) Published
JNK/SAPKs are identified as new members of the MAPK family; they phosphorylate c-Jun protein in response to several cellular stimuli including ultraviolet irradiation, TNF and osmotic shock. We have identified a protein kinase, MUK, as an activator of the JNK-pathway, whose kinase domain shows significant homology to MAPKKK-related proteins such as c-Raf and MEKK. The over-expression of MUK or MEK kinase (MEKK) in NIH3T3 or COS1 cells results in the activation of JNK1 and the accumulation of a hyper-phosphorylated form of c-Jun. While MEKK also activates the ERK pathway, MUK is a rather selective activator of the JNK pathway. On the other hand, c-Raf activates the JNK pathway only slightly despite its remarkable ability to activate the ERK pathway. Even though we originally identified MUK as a MAPKKK-related protein kinase, a greater similarity to mixed lineage kinase (MLK) is found not only in the catalytic domain but also in the 'leucine-zipper'-like motifs located at the C-terminal side of the catalytic domain. The structural divergence between MUK and MEKK reveals the multiplicity of signaling pathways that activate JNK/SAPKs.
Place, publisher, year, edition, pages
Nature Publishing Group, 1996. Vol. 12, no 3, 641-650 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-98850PubMedID: 8637721OAI: oai:DiVA.org:liu-98850DiVA: diva2:656001