MKK7 is an essential component of the JNK signal transduction pathway activated by proinflammatory cytokines

UMMS Affiliation

Howard Hughes Medical Institute; Department of Cancer Biology; Department of Cell Biology; Program in Molecular Medicine

Publication Date


Document Type



Animals; Cells, Cultured; Cytokines; Embryo, Mammalian; Fibroblasts; Fluorescent Antibody Technique; Immunoblotting; Interleukin-1; *JNK Mitogen-Activated Protein Kinases; *MAP Kinase Kinase 4; MAP Kinase Kinase 7; Mice; Mitogen-Activated Protein Kinase Kinases; Phosphorylation; *Signal Transduction; Tumor Necrosis Factor-alpha


Life Sciences | Medicine and Health Sciences


Mitogen-activated protein kinases (MAPK) are activated by phosphorylation on Thr and Tyr by MAPK kinases. Two MAPK kinases (MKK4 and MKK7) can activate the c-Jun NH(2)-terminal kinase (JNK) group of MAPK in vitro. JNK is phosphorylated preferentially on Tyr by MKK4 and on Thr by MKK7. Targeted gene-disruption studies in mice were performed to examine the role of MKK4 and MKK7 in vivo. Simultaneous disruption of the Mkk4 and Mkk7 genes was required to block JNK activation caused by exposure of cells to environmental stress. In contrast, disruption of the Mkk7 gene alone was sufficient to prevent JNK activation caused by proinflammatory cytokines. These data demonstrate that MKK4 and MKK7 serve different functions in the JNK signal transduction pathway.

DOI of Published Version



Genes Dev. 2001 Jun 1;15(11):1419-26. Link to article on publisher's site

Journal/Book/Conference Title

Genes and development

Related Resources

Link to Article in PubMed

PubMed ID