Nigg E A, Gallant P, Krek W
Swiss Institute for Experimental Cancer Research (ISREC), Epalinges.
Ciba Found Symp. 1992;170:72-84; discussion 84-96. doi: 10.1002/9780470514320.ch6.
Activation of the protein kinase p34cdc2 is required for entry into meiotic or mitotic M phase in all eukaryotic cells. One important mechanism regulating the activity of p34cdc2 during the cell cycle is based on phosphorylation/dephosphorylation. Avian p34cdc2 is phosphorylated on threonine 14 (Thr14), tyrosine 15 (Tyr15), threonine 161 (Thr161) and serine 277 (Ser277). Dephosphorylation of both Thr14 and Tyr15 is required for activation of p34cdc2 at the G2/M transition, indicating that phosphorylation of these residues negatively regulates p34cdc2 activity. Conversely, phosphorylation of Thr161 is required for kinase activity. Whether modification of this residue is due to intramolecular autophosphorylation or to the action of an as yet unidentified kinase remains unresolved. Likewise, the role of phosphorylation of p34cdc2 on Ser277 during G1 phase of the cell cycle remains to be determined. The function of p34cdc2 is regulated also by cell cycle-dependent complex formation with cyclin proteins. We found that chicken cyclin B2 undergoes a striking redistribution from the cytoplasm to the nucleus just prior to the onset of mitosis. Expression of a non-destructible cyclin B2 mutant causes HeLa cells to arrest in mitosis. Frequently, arrested cells displayed multiple mitotic spindles.
在所有真核细胞中，进入减数分裂或有丝分裂M期都需要蛋白激酶p34cdc2的激活。在细胞周期中调节p34cdc2活性的一个重要机制是基于磷酸化/去磷酸化。禽类p34cdc2在苏氨酸14（Thr14）、酪氨酸15（Tyr15）、苏氨酸161（Thr161）和丝氨酸277（Ser277）上发生磷酸化。在G2/M期转换时，Thr14和Tyr15的去磷酸化是p34cdc2激活所必需的，这表明这些残基的磷酸化对p34cdc2活性起负调节作用。相反，Thr161的磷酸化是激酶活性所必需的。该残基的修饰是由于分子内自磷酸化还是尚未鉴定的激酶的作用仍未解决。同样，在细胞周期的G1期，p34cdc2在Ser277上的磷酸化作用仍有待确定。p34cdc2的功能也通过与细胞周期蛋白形成依赖于细胞周期的复合物来调节。我们发现，鸡细胞周期蛋白B2在有丝分裂开始前从细胞质到细胞核发生了显著的重新分布。不可破坏的细胞周期蛋白B2突变体的表达导致HeLa细胞停滞在有丝分裂期。停滞的细胞经常显示出多个有丝分裂纺锤体。
