首页> 外文期刊>The Korean Journal of Genetics >Homo- and Hetero-Dimerization of Homeodomain-Interacting Protein Kinases (fflPKs)
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Homo- and Hetero-Dimerization of Homeodomain-Interacting Protein Kinases (fflPKs)

机译:同源域和异源二聚体相互作用的同源蛋白激酶(fflPKs)。

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Homeodomain-interacting protein kinases (HIPKs) constitute a novel family of nuclear protein kinases which function as crucial regulators of apoptosis and cell fate determination during development. Despite the important functions of HIPKs in the context of both UV- and stress-induced apoptosis and cell growth control, there remains little available data with regard to the biochemical properties of HIPKs. Here we show that HIPK1 and IHPK2 are able to both homo- and hetero-dimerize through their C-terminal regions, and to colocalize in the nuclear dots. Treatment of in vitro-translated HIPKl and HIPK2 with disuccinimidyl suberate (DSS), a chemical cross-linking reagent, was shown to result in the homo-dimerization of HIPK1 and HIPK2, respectively. Yeast two-hybrid domain analysis revealed that the C-terminal portion of HIPK2 was responsible for its dimerization. Furthermore, HIPK2 was also determined to immunoprecipitate with HIPK2 and HIPK1, indicating the homo- and hetero-association of both H1PK2and HIPK1 in cultured cells. However, the catalytic activities of HIPK1/HIPK2 hetero-dimer with regard to auto-phosphorylation and substrate-phosphorylation were less pronounced than those of the HIPK2 homo-dimer. Consistent with the formation of the HIPKl/2 hetero-dimer, HIPK2 was also found to colocalize with HIPK1 in the nuclear dots. These results suggest that cross-talk takes place between the HIPKs, which exploit a variety of mechanisms in the regulation of HIPK activity.
机译:Homeodomain相互作用蛋白激酶(HIPKs)构成了一个新的核蛋白激酶家族,在发育过程中作为凋亡和细胞命运决定的关键调节剂。尽管HIPK在紫外线和应激诱导的细胞凋亡和细胞生长控制的背景下起着重要的作用,但是关于HIPK的生化特性仍然缺乏可用的数据。在这里,我们显示HIPK1和IHPK2能够通过其C端区域进行均二聚和异源二聚化,并能够共定位于核点中。已显示用辛二酸二琥珀酰亚胺酯(DSS)(一种化学交联剂)处理体外翻译的HIPK1和HIPK2分别导致HIPK1和HIPK2的均二聚。酵母两杂交域分析表明,HIPK2的C端部分负责其二聚化。此外,还确定了HIPK2与HIPK2和HIPK1发生免疫沉淀,这表明在培养细胞中HIPK2和HIPK1的同源和异源关联。但是,HIPK1 / HIPK2异二聚体在自磷酸化和底物磷酸化方面的催化活性不如HIPK2均二聚体。与HIPK1 / 2异二聚体的形成一致,还发现HIPK2与HIPK1在核点中共定位。这些结果表明,HIPK之间发生了串扰,HIPK在调节HIPK活性方面采用了多种机制。

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