蛋白質磷酸酶2A型 (以下簡稱PP2A)是由三種次單元所組成，包含了具有PP2A酵素活性的催化次單元C、做為骨架功能的結構次單元A、以及最為多樣化的調節性次單元B。不同的B次單元被認為具有決定PP2A完全酶的受質特異性、生長發育的調節以及在細胞中坐落的位置。至今最少已發現四種調節性次單元家族，分別為B、B’、B’’以及B’’’。
首先，我們藉由間接免疫染色法的方式，發現在NIH3T3細胞中短暫表現A次單元的分布情形是以cytoplasm為主，少部分細胞呈現均勻分布的現象。而在短暫表現C次單元時可以觀察到，C次單元在細胞各處皆有表現，但主要仍是以 cytoplasm的分布為最多。接著，我們也對於最為多變化的B次單元在細胞中的分布情形進行研究，包含B55α、B55β1、B55β2、B55δ與B56γ3。結果顯示，單獨表現B55α或B55δ的分布情形主要皆坐落在cytoplasm的位置，而B55β1與B56γ3則是以核質均勻的分布方式為主要代表，B55β2則有分布類似於mitochondria的情形。此外，在B55β1 N-terminal部分序列換成B55α N-terminal的部分特異序列的B55βαβ混合體，其分布位置則傾向於類似B55α的分布。
接下來，我們藉由雙分子螢光互補法(BiFC)的方式來探討PP2A完全酶在細胞中的分布位置。首先，我們藉由BiFC方法所產生的螢光表現，可以直接觀察到A與C 次單元結合時的分布位置，主要是以核質均勻或是質多於核的方式呈現。我們也利用BiFC方法來探討，Aα 次單元與各種不同的B次單元結合後在細胞中的分布情形。將以上直接觀察A與B次單元交互作用後所得到的BiFC的螢光結果，與利用間接免疫螢光染色法得到的單獨表現B次單元的分布情形進行比較後，分布位置具有一致的結果。進一步，我們利用能夠與B次單元競爭Aα 次單元結合的腫瘤病毒SV40的small T抗原(ST)，證實了Aα與B次單元經交互作用後所產生的BiFC現象是具有特異性的。此外，我們也藉由BiFC這個方法證實在細胞週期S-phase時，A與B56γ3結合後，會有在細胞核高度表現的情形，然而B55則不會。
總結來說，我們成功建立BiFC方法致力於研究PP2A A、B、C次單元在細胞中交互作用的情形，並且我們的結果進一步驗證了，B次單元對於PP2A在細胞中分佈的位置具有決定性角色的理論。

Protein phosphatase 2A (PP2A) is a heterotrimeric enzyme consisting of a catalytic subunit (C), a scaffolding subunit (A), and a variable regulatory subunit (B). The regulatory subunit B is believed to determine the substrate specificity, developmental regulation, and subcellular localization of the PP2A holoenzymes, and there are at least four different families of the regulatory subunit, termed B, B’, B’’ and B’’’ families.
By indirect immunofluorescence microscopy, we found that in NIH3T3 cells transiently expressed A subunits displayed a mainly cytoplasmic distribution pattern, with a few cells displaying ubiquitous distribution. Distribution of transiently expressed C subunits was mainly ubiquitous throughout the cell, with some cells exhibiting a primarily cytoplasmic pattern. Analyses of subcellular localization of transiently expressed B subunits, including B55, B55β1, B55β2, B55δ, and B56γ3, demonstrated that B55 and B55δ were primarily cytoplasmic, and that B55β1 and B56γ3 showed mainly ubiquitous distribution. In addition, B55β2 seemed to localize to the mitochondria. More, B55ββ, which is a B55β1 with part of its N-terminal sequence substituted with the most unique N-terminal sequence of B55, showed a distribution pattern similar to that of B55 rather than B55β1.
Further, we employed bimolecular fluorescence complementation (BiFC) analysis to investigate the subcellular localization of the PP2A holoenzymes. Firstly, we found that association of the A and C subunits exhibited either a ubiquitous pattern of fluorescence or a cytoplasmic pattern of fluorescence due to BiFC. Secondly, we showed that association of the A subunit with various B subunits exhibited distinct subcellular distribution of fluorescence due to BiFC, consistent with results of indirect immunofluorescence analysis for individual B subunits. Thirdly, we demonstrated the specificity of fluorescence caused by BiFC resulting from specific interactions between the A and B subunits by employing small T antigen (ST) of tumor virus SV40 which competes with B subunit for binding with the A subunits. Furthermore, we demonstrated that association of A and B56γ3, but not B55, was highly enriched in the nucleus during S phase using BiFC analysis.
In summary, we successfully established BiFC analyses to investigate interactions between the PP2A A, B and C subunits in cells, and our results confirmed that the regulatory B subunits indeed play a dominant role in determining the subcellular localization of the PP2A.

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