Two novel phosphatidylinositol-4-phosphate 5-kinase type Igamma splice variants expressed in human cells display distinctive cellular targeting.
Two novel phosphatidylinositol-4-phosphate 5-kinase type Igamma splice variants expressed in human cells display distinctive cellular targeting.
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DOI：
10.1042/bj20090638
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发表时间：
2009-08-27
期刊：
影响因子：
--
通讯作者：
Anderson RA
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文献类型：
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作者：
Schill NJ;Anderson RA
细胞内不同位置的各种磷酸肌醇信使分子的产生是通过磷酸肌醇激酶的不同亚型和剪接变体的特异性靶向来介导的。当靶向不同的细胞区室时，其中几种酶会产生脂质信使 PtdIns(4,5)P2。 PIPK（PtdIns4P 5-激酶）的 Iγ 型同工型的几种剪接变体已被鉴定，可生成 PtdIns(4,5)P2，并且每种剪接变体被认为在细胞内发挥着独特的功能作用。在这里，我们在人类细胞中鉴定了两种新的 PIPKIγ C 端剪接变体，由 700 和 707 个氨基酸组成。这两种剪接变体在多种组织类型中表达，并在体外表现出 PIPK 活性。有趣的是，这两种新的剪接变体都显示出不同的亚细胞靶向性。加上这两种新的剪接亚型，在哺乳动物中至少已鉴定出五种 PIPKIγ 剪接变体。因此，我们建议使用 HUGO（人类基因组组织）命名法来命名剪接亚型。 PIPKIγ_i4（700 个氨基酸）存在于细胞核中，这是一种之前在任何 PIPKIγ 剪接变体中未观察到的靶向模式。 PIPKIγ_i5（707 个氨基酸）靶向细胞内囊泡样结构，与几种类型的内体区室的标记物共定位。与其他 PIPKIγ 剪接变体一样，PIPKIγ_i4 和 PIPKIγ_i5 独特的 C 端序列可能有助于与独特的蛋白质靶向因子关联，从而将激酶定位到其适当的细胞亚结构域，以进行 PtdIns(4,5)P2 的位点特异性生成。
The generation of various phosphoinositide messenger molecules at distinct locations within the cell is mediated via the specific targeting of different isoforms and splice variants of phosphoinositide kinases. The lipid messenger PtdIns(4,5)P2 is generated by several of these enzymes when targeted to distinct cellular compartments. Several splice variants of the type Iγ isoform of PIPK (PtdIns4P 5-kinase), which generate PtdIns(4,5)P2, have been identified, and each splice variant is thought to serve a unique functional role within cells. Here, we have identified two novel C-terminal splice variants of PIPKIγ in human cells consisting of 700 and 707 amino acids. These two splice variants are expressed in multiple tissue types and display PIPK activity in vitro. Interestingly, both of these novel splice variants display distinct subcellular targeting. With the addition of these two new splice isoforms, there are minimally five PIPKIγ splice variants that have been identified in mammals. Therefore, we propose the use of the HUGO (Human Genome Organization) nomenclature in the naming of the splice isoforms. PIPKIγ_i4 (700 amino acids) is present in the nucleus, a targeting pattern that has not been previously observed in any PIPKIγ splice variant. PIPKIγ_i5 (707 amino acids) is targeted to intracellular vesicle-like structures, where it co-localizes with markers of several types of endosomal compartments. As occurs with other PIPKIγ splice variants, the distinctive C-terminal sequences of PIPKIγ_i4 and PIPKIγ_i5 may facilitate association with unique protein targeting factors, thereby localizing the kinases to their appropriate cellular subdomains for the site-specific generation of PtdIns(4,5)P2.