Active nucleocytoplasmic shuttling required for function and regulation of stress-activated kinase Spc1/StyI in fission yeast
Active nucleocytoplasmic shuttling required for function and regulation of stress-activated kinase Spc1/StyI in fission yeast
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DOI：
10.1091/mbc.10.5.1395
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发表时间：
1999-05-01
影响因子：
3.3
通讯作者：
Russell, P
中科院分区：
文献类型：
--
作者：
Gaits, F;Russell, P
许多应激反应基因的转录诱导依赖于应激诱导的应激激活蛋白激酶(SAPKs)的核积聚。在裂殖酵母中，SAPK SPc1(也称为StyI)的核积累需要SAPK激酶Wis1催化的磷酸化，但目前尚不清楚SPc1的定位是否受核运输因子的调控。有研究表明，在渗透胁迫过程中，SPc1的定位受到主动转运机制的调节。SPc1的核进口需要Pim1，它是鸟嘌呤核苷酸交换因子RCC1的同系物，对蛋白质的核质穿梭是必不可少的。SPc1的核出口受出口系数CRM1管制。当Spc1从细胞核中输出时，会形成Spc1-CRM1复合体。WIS1和使SPc1失活的酪氨酸磷酸酶Pyp1和Pyp2通过不依赖CRM1的机制被排除在细胞核之外；因此，SPc1的核输入导致了从其调控蛋白中瞬时分离。因此，在渗透性休克反应中，SPc1的功能和调节都需要主动的核质穿梭。
Transcriptional induction of many stress-response genes is dependent on stress-induced nuclear accumulation of stress-activated protein kinases (SAPKs). In the fission yeast Schizosaccharomyces pombe, nuclear accumulation of the SAPK Spc1 (also known as StyI) requires activating phosphorylation catalyzed by the SAPK kinase Wis1; however, it is unknown whether the localization of Spc1 is regulated by nuclear transport factors. Herein are reported studies that show that Spc1 localization is regulated by active transport mechanisms during osmotic stress. Nuclear import of Spc1 requires Pim1, a homologue of the guanine nucleotide exchange factor RCC1 that is essential for nucleocytoplasmic shuttling of proteins. Nuclear export of Spc1 is regulated by the export factor Crm1. An Spc1-Crm1 complex forms as Spc1 is exported from the nucleus. Wis1 and the tyrosine phosphatases Pyp1 and Pyp2 that inactivate Spc1 are excluded from the nucleus by a Crm1-independent mechanism; hence the nuclear import of Spc1 leads to transient isolation from its regulatory proteins. Thus, active nucleocytoplasmic shuttling is required for both the function and regulation of Spc1 during the osmotic shock response.