Chen M, Cooper J A
Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Proc Natl Acad Sci U S A. 1997 Aug 19;94(17):9136-40. doi: 10.1073/pnas.94.17.9136.
CKII (formerly known as casein kinase II) is a ubiquitously expressed enzyme that plays an important role in regulating cell growth and differentiation. The beta subunit of CKII (CKIIbeta) is not catalytic but forms heterotetramers with the catalytic subunit alpha to generate an alpha2beta2 holoenzyme. In Xenopus oocytes, CKIIbeta also associates with another serine/threonine kinase, Mos. As a key regulator of meiosis, Mos is necessary and sufficient to initiate oocyte maturation. We have previously shown that the binding of CKIIbeta to Mos represses Mos-mediated mitogen-activated protein kinase (MAPK) activation and that the ectopic expression of CKIIbeta inhibits progesterone-induced Xenopus oocyte maturation. We have now used an antisense oligonucleotide technique to reduce the endogenous CKIIbeta protein level in Xenopus oocytes, and we find that oocytes with a reduced content of CKIIbeta are more sensitive to low doses of progesterone and show accelerated MAPK activation and germinal vesicle breakdown. Furthermore, ectopic expression of a Mos-binding fragment of CKIIbeta suppressed the effect of antisense oligonucleotide. These results suggest that the endogenous CKIIbeta normally sets a threshold level for Mos protein, which must be exceeded for Mos to activate the MAPK signaling pathway and induce oocyte maturation.
CKII(以前称为酪蛋白激酶II)是一种广泛表达的酶,在调节细胞生长和分化中起重要作用。CKII的β亚基(CKIIβ)没有催化活性,但与催化亚基α形成异源四聚体,以产生α2β2全酶。在非洲爪蟾卵母细胞中,CKIIβ还与另一种丝氨酸/苏氨酸激酶Mos相互作用。作为减数分裂的关键调节因子,Mos对于启动卵母细胞成熟是必需且充分的。我们之前已经表明,CKIIβ与Mos的结合会抑制Mos介导的丝裂原活化蛋白激酶(MAPK)激活,并且CKIIβ的异位表达会抑制孕酮诱导的非洲爪蟾卵母细胞成熟。我们现在使用反义寡核苷酸技术降低非洲爪蟾卵母细胞中内源性CKIIβ蛋白水平,并且我们发现CKIIβ含量降低的卵母细胞对低剂量孕酮更敏感,并且显示出加速的MAPK激活和生发泡破裂。此外,CKIIβ的Mos结合片段的异位表达抑制了反义寡核苷酸的作用。这些结果表明,内源性CKIIβ通常为Mos蛋白设定一个阈值水平,Mos必须超过该阈值才能激活MAPK信号通路并诱导卵母细胞成熟。