Novel function of MKP-5/DUSP10, a phosphatase of stress-activated kinases, on ERK-dependent gene expression, and upregulation of its gene expression in colon carcinomas.

Novel function of MKP-5/DUSP10, a phosphatase of stress-activated kinases, on ERK-dependent gene expression, and upregulation of its gene expression in colon carcinomas.

Oncology reports (2012-06-20)

Miyuki Nomura, Ken-Ichi Shiiba, Chiaki Katagiri, Isao Kasugai, Kouhei Masuda, Ikuro Sato, Masayuki Sato, Yoichiro Kakugawa, Eiki Nomura, Katsuhisa Hayashi, Yoshihiro Nakamura, Toshiyuki Nagata, Tsunayuki Otsuka, Ryuichi Katakura, Yoji Yamashita, Masami Sato, Nobuhiro Tanuma, Hiroshi Shima

PMID22711061

摘要

Mitogen-activated protein kinase phosphatase 5 (MKP-5)/DUSP10 acts as a phosphatase of stress-activated kinases (JNK and p38), but its activity towards ERK has not been demonstrated. In the present study we observed that MKP-5 interacts with ERK, retains it in the cytoplasm, suppresses its activation and downregulates ERK-dependent transcription. These data suggested a novel MKP-5 function as a scaffold protein for the ERK pathway. We analyzed MKP-5 gene expression in several tumors, and found that it is frequently upregulated in colorectal but not in lung and breast cancer, suggesting its association with the malignant phenotype of colon cancer.