Nucleocytoplasmic shuttling of STK16 (PKL12), a Golgi-resident serine/threonine kinase involved in VEGF expression regulation
Nucleocytoplasmic shuttling of STK16 (PKL12), a Golgi-resident serine/threonine kinase involved in VEGF expression regulation
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DOI：
10.1016/j.yexcr.2005.10.010
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发表时间：
2005-01-15
影响因子：
3.7
通讯作者：
Bernad, A
中科院分区：
文献类型：
--
作者：
Guinea, B;Ligos, JM;Bernad, A
PKL 12/STK 16蛋白是第一个被发现的哺乳动物ser/thr激酶亚家族成员，该亚家族在多个王国中保守，在小鼠组织和细胞类型中具有广泛的表达模式。内源性STK 16亚细胞定位通过间接免疫荧光法在NIH/3 T3和NRK细胞中进行了评价，证明了高尔基体相关的模式似乎独立于整联蛋白途径提供的信号。当用brereldin A（BFA）或nocodazole（促进高尔基体解体的药物）处理细胞时，我们观察到STK 16易位到核区室。逆转录病毒载体对这种蛋白质的组成性过表达也促进了STK 16在核区室中的积累，如亚分级分离研究所示。一个激酶死亡的STK 16突变体（E202 A）被用来证明，高尔基体协会和核转位能力似乎是独立的STK 16激酶活性。此外，我们发现STK 16在几种细胞系中的过表达增强了它们产生和分泌VEGF的能力。为了在体内证实这些数据，我们将过表达STK 16的肿瘤细胞注射到免疫缺陷的BALBc/SCID小鼠中。与对照相比，过表达STK 16的HT 1080衍生的肿瘤显示出血管体积和数量增加。总之，这些数据与先前的报告一致，表明STK 16作为转录共激活因子的潜在作用。(c)2005年爱思唯尔公司All rights reserved.
PKL12/STK 16 protein is the first identified mammalian member of a ser/thr kinase subfamily that is conserved across several kingdoms, with a broad expression pattern in murine tissues and cell types. Endogenous STK16 subcellular localization was evaluated by indirect immunofluorescence in NIH/3T3 and NRK cells, demonstrating a Golgi-associated pattern that appears to be independent of signals provided by integrin pathways. When cells were treated with brereldin A (BFA) or nocodazole, drugs that promote Golgi disorganization, we observed STK16 translocation to the nuclear compartment. Constitutive overexpression of this protein by retroviral vectors also promotes accumulation of STK16 in the nuclear compartment, as shown by subfractionation Studies. A kinase-dead STK16 mutant (E202A)was used to demonstrate that both the Golgi association and the nuclear translocation capabilities seem to be independent of the STK16 kinase activity. In addition, we show that STK16 overexpression in several cell lines enhances their capacity to produce and secrete VEGF. To confirm these data in vivo, we injected tumor cells overexpressing STK16 into immunodeficient BALBc/SCID mice. HT1080-derived tumors overexpressing STK16 showed increased volume and number of blood vessels compared to controls. Altogether, these data concur with previous reports suggesting a potential role for STK16 as a transcriptional co-activator. (c) 2005 Elsevier Inc. All rights reserved.