Atypical protein kinase Cλ binds and regulates p70 S6 kinase
Atypical protein kinase Cλ binds and regulates p70 S6 kinase
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DOI：
10.1042/bj3350417
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发表时间：
1998-10-15
影响因子：
4.1
通讯作者：
Ohno, S
中科院分区：
文献类型：
--
作者：
Akimoto, K;Nakaya, M;Ohno, S
p70 S6激酶（p70 S6K）参与细胞周期进程的调节。然而，其激活机制尚不完全清楚。在目前的工作中，有证据表明，非典型蛋白激酶C （PKC）的同型PKC lambda对于p70 S6K的激活是必不可少的，但不是充分的。PKC lambda的调控结构域和激酶结构域都与p70 S6K直接相关。无激酶活性的激酶结构域或PKC lambda的调控结构域的过表达导致血清诱导的p70 S6K的激活受到抑制。此外，PKC lambda的两种显性阴性突变体以及p70 S6K的激酶缺陷突变体抑制血清诱导的DNA合成和E2F激活。然而，活性形式PKC lambda的过表达不能激活p70 S6K。这些结果表明，PKC lambda是调节p70 S6K活性的中介，在细胞周期进程中起重要作用。
p70 S6 kinase (p70 S6K) has been implicated in the regulation of cell cycle progression. However, the mechanism of its activation is not fully understood. In the present work, evidence is provided that an atypical protein kinase C (PKC) isotype, PKC lambda, is indispensable, but not sufficient, for the activation of p70 S6K. Both the regulatory and kinase domains of PKC lambda associate directly with p70 S6K. Overexpression of the kinase domain without kinase activity or the regulatory domain of PKC lambda results in the suppression of the serum-induced activation of p70 S6K. In addition, two types of dominant-negative mutants of PKC lambda, as well as a kinase-deficient mutant of p70 S6K, suppress serum-induced DNA synthesis and E2F activation. The overexpression of the active form of PKC lambda, however, fails to activate p70 S6K. These results suggest that PKC lambda is a mediator in the regulation of p70 S6K activity and plays an important role in cell cycle progression.