Regulation of Translation During In Vitro Maturation of Bovine Oocytes: The Role of MAP Kinase, eIF4E (Cap Binding Protein) Phosphorylation, and eIF4E-BP11
Regulation of Translation During In Vitro Maturation of Bovine Oocytes: The Role of MAP Kinase, eIF4E (Cap Binding Protein) Phosphorylation, and eIF4E-BP11
复制标题
牛卵母细胞体外成熟过程中翻译的调控：MAP 激酶、eIF4E（帽结合蛋白）磷酸化和 eIF4E-BP11 的作用
作者：
W. Tomek;F. Sterza;M. Kubelka;K. Wollenhaupt;H. Torner;M. Anger;W. Kanitz
摘要哺乳动物卵母细胞减数分裂成熟（从前期Ⅰ到中期Ⅱ的转变）伴随着蛋白质磷酸化模式的复杂变化。至少有两个主要的蛋白激酶参与这些事件，即cdc 2激酶和促分裂原活化蛋白（MAP）激酶，因为这些激酶的抑制逮捕哺乳动物卵母细胞在萌发囊泡（GV）阶段。我们发现，在牛卵母细胞减数分裂成熟过程中，翻译起始因子eIF 4 E（帽结合蛋白），逐渐变得磷酸化。这种实质性的磷酸化开始于胚泡破裂（GVBD）的时间，并持续到中期II阶段。eIF 4 E磷酸化的发生与整体蛋白质合成的显著增加平行。然而，虽然eIF 4 E在中期II卵母细胞中几乎完全磷酸化，但蛋白质合成在此阶段仅达到基础水平，类似于前期I卵母细胞，其中该因子保持未磷酸化。我们目前的证据表明，一个特定的阻遏物eIF 4 E，结合蛋白4 E-BP 1，是存在的，并可能参与防止eIF 4 E功能在中期II阶段卵母细胞。最近，两种蛋白激酶，称为Mnk 1和Mnk 2，已被确定在体细胞中作为eIF 4 E激酶，这两种激酶都是MAP激酶在体内的底物。在牛卵母细胞中，cdk激酶的特异性抑制剂丁内酯I将卵母细胞阻滞在GV期，并阻止cdc 2和MAP激酶的激活。在这些条件下，eIF 4 E的磷酸化也被阻断，其在翻译起始中的功能受损。相比之下，PD 098059是MAP激酶活化途径的特异性抑制剂，其抑制MAP激酶激酶（称为MEK功能），仅导致GVBD延迟，以及MAP激酶和eIF 4 E磷酸化延迟。这些结果表明，在牛卵母细胞中，1）MAP激酶活化仅部分依赖于MEK激酶，2）MAP激酶参与eIF 4 E磷酸化，3）完全磷酸化的eIF 4 E的丰度不一定直接刺激蛋白质合成。一个可能的MEK激酶独立的MAP激酶磷酸化途径和4 E-BP 1在抑制中期II卵母细胞翻译的作用进行了讨论。
Abstract Meiotic maturation of mammalian oocytes (transition from prophase I to metaphase II) is accompanied by complex changes in the protein phosphorylation pattern. At least two major protein kinases are involved in these events; namely, cdc2 kinase and mitogen-activated protein (MAP) kinase, because the inhibition of these kinases arrest mammalian oocytes in the germinal vesicle (GV) stage. We show that during meiotic maturation of bovine oocytes, the translation initiation factor, eIF4E (the cap binding protein), gradually becomes phosphorylated. This substantial phosphorylation begins at the time of germinal vesicle breakdown (GVBD) and continues to the metaphase II stage. The onset of eIF4E phosphorylation occurs in parallel with a significant increase in overall protein synthesis. However, although eIF4E is nearly fully phosphorylated in metaphase II oocytes, protein synthesis reaches only basal levels at this stage, similar to that of prophase I oocytes, in which the factor remains unphosphorylated. We present evidence that a specific repressor of eIF4E, the binding protein 4E-BP1, is present and could be involved in preventing eIF4E function in metaphase II stage oocytes. Recently, two protein kinases, called Mnk1 and Mnk2, have been identified in somatic cells as eIF4E kinases, both of which are substrates of MAP kinase in vivo. In bovine oocytes, a specific inhibitor of cdk kinases, butyrolactone I, arrests oocytes in GV stage and prevents activation of both cdc2 and MAP kinase. Under these conditions, the phosphorylation of eIF4E is also blocked, and its function in initiation of translation is impaired. In contrast, PD 098059, a specific inhibitor of the MAP kinase activation pathway, which inhibits the MAP kinase kinase, called MEK function, leads only to a postponed GVBD, and a delay in MAP kinase and eIF4E phosphorylation. These results indicate that in bovine oocytes, 1) MAP kinase activation is only partially dependent on MEK kinase, 2) MAP kinase is involved in eIF4E phosphorylation, and 3) the abundance of fully phosphorylated eIF4E does not necessarily directly stimulate protein synthesis. A possible MEK kinase-independent pathway of MAP kinase phosphorylation and the role of 4E-BP1 in repressing translation in metaphase II oocytes are discussed.
登录
查看更多内容
DOI：
10.1016/s0021-9258(19)39637-1
发表时间：
1990-03
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
R. Kaspar;W. Rychlik;M. White;R. Rhoads;D. Morris
通讯作者：
R. Kaspar;W. Rychlik;M. White;R. Rhoads;D. Morris
蛋白激酶 C 或多能 S6 激酶对 eIF-4F 的磷酸化可在起始时刺激蛋白质合成。
DOI：
--
发表时间：
1991
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Morley,SJ;Dever,TE;Etchison,D;Traugh,JA
通讯作者：
Traugh,JA
影响因子：
56.9
作者：
LIN, TA;KONG, XM;LAWRENCE, JC
通讯作者：
LAWRENCE, JC
影响因子：
10.5
作者：
Gingras, AC;Gygi, SP;Sonenberg, N
通讯作者：
Sonenberg, N
影响因子：
2.7
作者：
BORNSLAEGER, EA;MATTEI, P;SCHULTZ, RM
通讯作者：
SCHULTZ, RM