Nebreda A R, Hill C, Gomez N, Cohen P, Hunt T
Imperial Cancer Research Fund Clare Hall Laboratories, South Mimms, Herts, UK.
FEBS Lett. 1993 Oct 25;333(1-2):183-7. doi: 10.1016/0014-5793(93)80401-f.
The mos protooncogene encodes a serine/threonine protein kinase that is only expressed at significant levels in germ cells. Recombinant malE-mos protein (Xenopus mos protooncogene fused in frame to the maltose binding protein of E. coli) activates MAP kinase in cell-free extracts prepared from Xenopus oocytes and eggs. Here we show that malE-mos immunoprecipitates from Xenopus extracts phosphorylate and activate MAP kinase kinase in vitro, indicating that mos can function as a MAP kinase kinase kinase. Moreover, ectopic expression of mos in mammalian somatic cells, that lack any endogenous mos protein, triggers the activation of MAP kinase in vivo. These results identify the mos protooncogene as a direct activator of the MAP kinase pathway, with the potential to activate this kinase cascade even in cells where normally there is no expression of mos.
mos原癌基因编码一种丝氨酸/苏氨酸蛋白激酶,该激酶仅在生殖细胞中大量表达。重组malE-mos蛋白(非洲爪蟾mos原癌基因与大肠杆菌麦芽糖结合蛋白读码框融合)可在从非洲爪蟾卵母细胞和卵子制备的无细胞提取物中激活丝裂原活化蛋白激酶(MAP激酶)。在此我们表明,从非洲爪蟾提取物中免疫沉淀的malE-mos在体外可磷酸化并激活MAP激酶激酶,这表明mos可作为MAP激酶激酶激酶发挥作用。此外,在缺乏任何内源性mos蛋白的哺乳动物体细胞中异位表达mos,可在体内触发MAP激酶的激活。这些结果确定mos原癌基因是MAP激酶途径的直接激活剂,甚至在通常不表达mos的细胞中也有激活该激酶级联反应的潜力。