Role and regulation of 90 kDa ribosomal S6 kinase (RSK) in signal transduction
Role and regulation of 90 kDa ribosomal S6 kinase (RSK) in signal transduction
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DOI：
10.1016/s0303-7207(99)00061-1
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发表时间：
1999-05-25
影响因子：
4.1
通讯作者：
Gammeltoft, S
中科院分区：
文献类型：
--
作者：
Frödin, M;Gammeltoft, S
细胞外信号激活丝裂原活化蛋白激酶（MAPK）级联以执行复杂的细胞程序，如增殖、分化和凋亡。在哺乳动物细胞中，已经表征了三个MAPK家族：细胞外信号调节激酶（ERK），其由生长因子、肽激素和神经递质激活，以及Jun激酶（JNK）和p38 MAPK，其由细胞应激刺激以及生长因子激活。本文综述了90 kDa核糖体S6激酶（RSK;也称为p90（RSK）或MAPK活化蛋白激酶-1，MAPKAP-K1）家族，它们是ERK的第一个底物被发现，并已被证明是ERK信号转导的普遍存在和多功能介体。RSK由两个功能性激酶结构域组成，其通过一系列磷酸化以顺序方式激活。最近，发现了一个由ERK和p38 MAPK激活的RSK相关激酶家族，并将其命名为丝裂原和应激激活蛋白激酶（MSK）。已经提出了RSK的许多细胞功能。(1)通过c-Fos、雌激素受体、NF κ B/I κ B α、cAMP反应元件结合蛋白（CREB）和CREB结合蛋白等转录调节因子的结合和磷酸化调节基因表达：（2）RSK通过Myt 1蛋白激酶失活导致细胞周期蛋白依赖性激酶B34（cdc 2）活化参与非洲爪蟾卵母细胞的细胞周期调节;（3）RSK可通过磷酸化多核糖体蛋白和糖原合成酶激酶-3调节蛋白质合成;和（4）RSK磷酸化Ras GTP/GDP交换因子，Sos导致Ras-ERK途径的反馈抑制，（C）1999由Elsevier Science爱尔兰Ltd.出版。保留所有权利。
Extracellular signals activate mitogen-activated protein kinase (MAPK) cascades to execute complex cellular programs, like proliferation, differentiation and apoptosis. In mammalian cells, three MAPK families have been characterized: extracellular signal-regulated kinase (ERK), which is activated by growth factors, peptide hormones and neurotransmitters, and Jun kinase (JNK) and p38 MAPK, which are activated by cellular stress stimulus as well as growth factors. This review describes the family of 90 kDa ribosomal S6 kinases (RSK; also known as p90(rsk) or MAPK-activated protein kinase-1, MAPKAP-K1), which were among the first substrates of ERK to be discovered and which has proven to be a ubiquitous and versatile mediator of ERK signal transduction. RSK is composed of two functional kinase domains that are activated in a sequential manner by a series of phosphorylations. Recently, a family of RSK-related kinases that are activated by ERK as well as p38 MAPK were discovered and named mitogen- and stress-activated protein kinases (MSK). A number of cellular functions of RSK have been proposed. (1) Regulation of gene expression via association and phosphorylation of transcriptional regulators including c-Fos, estrogen receptor, NF kappa B/I kappa B alpha, cAMP-response element-binding protein (CREB) and CREB-binding protein; (2) RSK is implicated in cell cycle regulation in Xenopus laevis oocytes by inactivation of the Myt1 protein kinase leading to activation of the cyclin-dependent kinase B34(cdc2); (3) RSK may regulate protein synthesis by phosphorylation of polyribosomal proteins and glycogen synthase kinase-3; and (4) RSK phosphorylates the Ras GTP/GDP-exchange factor, Sos leading to feedback inhibition of the Ras-ERK pathway, (C) 1999 Published by Elsevier Science Ireland Ltd. All rights reserved.