Human Mitogen-activated Protein Kinase Kinase 4 as a Candidate Tumor Suppressor
作者： John M. Kyriakis , Srikanth Jammulapati , Sean V. Tavtigian , Michelle Baumgard , Paul Bartel
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摘要: Abstract Mitogen-activated protein kinases function in signal transduction pathways that are involved controlling key cellular processes many organisms. A mammalian member of this kinase family, MKK4/JNKK1/SEK1, has been reported to link upstream MEKK1 downstream stress-activated kinase/JNK1 and p38 mitogen-activated kinase. This pathway implicated the cytokine- stress-induced apoptosis a variety cell types. Here, we report two human tumor lines, derived from pancreatic carcinoma lung carcinoma, harbor homozygous deletions eliminate coding portions MKK4 locus at 17p, located approximately 10 cM centromeric p53. In addition, set 88 cancer lines prescreened for loss heterozygosity, detected nonsense three missense sequence variants pancreatic, breast, colon, testis cells. vitro biochemical assays revealed that, when stimulated by MEKK1, four five altered proteins lacked ability phosphorylate Thus, incidence mutations is 6 213 (∼3%). These findings suggest may as suppressor tumorigenesis or metastasis certain types
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