Cloning and expression of human mitogen-activated protein kinase kinase 7gamma1.

Mitogen-activated protein kinase kinase 7 (MKK7) is a direct activator of the mitogen-activated protein kinase family member c-Jun N-terminal kinase (JNK). MKK7 activates JNK via phosphorylation of a threonine and tyrosine residue in a Thr-Pro-Tyr motif within kinase subdomain VIII. To date at least six different isoforms of murine MKK7 have been identified. However, only three isoforms of human MKK7 have been reported. We report here the cloning of hMKK7gamma1, the human homolog of murine MKK7gamma1. Expression of hMKK7gamma1 mRNA was assessed and transcripts were present in low levels in placenta, fetal liver, and skeletal muscle. PCR results indicate that hMKK7gamma1 is expressed in various normal tissues, tumors, and in synoviocytes from rheumatoid and osteoarthritis patients. Recombinant hMKK7gamma1 can be phosphorylated and activated by MEKK1. Further studies will provide insight into the role for hMKK7gamma1 versus other MKK7 isoforms.