Mitogen-activated protein kinase kinase 4 (also known as MKK4)
399 amino acids; about 44 kDa
This gene encodes a dual specificity protein kinase that belongs to the Ser/Thr protein kinase family. This kinase is a direct activator of MAP kinases in response to various environmental stresses or mitogenic stimuli. It has been shown to activate MAPK8/JNK1, MAPK9/JNK2, and MAPK14/p38, but not MAPK1/ERK2 or MAPK3/ERK3. This kinase is phosphorylated, and thus activated by MAP3K1/MEKK. The knockout studies in mice suggested the roles of this kinase in mediating survival signal in T cell development, as well as in the organogenesis of liver.
Somatic MAP2K4 mutations (of which 40% are substitutions) have been found in tumors of endometrium (about 10% of cases), pancreas, breast, large intestine, biliary tract, testis, urinary tract, other less than 5%.
References (open access):
MKK4 as oncogene or tumor suppressor: in cancer and senescence, the story's getting old. Cunningham SC, Gallmeier E, Kern SE. Aging (Albany NY). 2010 Nov;2(11):752-3.
Association of genetic variation in mitotic kinases with breast cancer risk. Wang X, Fredericksen ZS, Vierkant RA, Kosel ML, Pankratz VS, Cerhan JR, Justenhoven C, Brauch H; GENICA Consortium, Olson JE, Couch FJ. Breast Cancer Res Treat. 2010 Jan;119(2):453-62.