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首页> 外文期刊>Molecular and Cellular Biology >TAPP1 and TAPP2 Are Targets of Phosphatidylinositol 3-Kinase Signaling in B Cells: Sustained Plasma Membrane Recruitment Triggered by the B-Cell Antigen Receptor
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TAPP1 and TAPP2 Are Targets of Phosphatidylinositol 3-Kinase Signaling in B Cells: Sustained Plasma Membrane Recruitment Triggered by the B-Cell Antigen Receptor

机译：TAPP1和TAPP2是B细胞中磷脂酰肌醇3-激酶信号转导的靶标：B细胞抗原受体触发的持续血浆膜募集。

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We report the characterization of two signal transduction proteins related to Bam32, known as TAPP1 and TAPP2. Bam32, TAPP1, and TAPP2 share several characteristics, including small size (32 to 47 kDa), lack of enzymatic domains, high conservation between humans and mice, and the presence of pleckstrin homology (PH) domains near their C termini which contain the 3-phosphoinositide-binding motif. Unlike Bam32, the N-terminal regions of TAPP1 and TAPP2 contain a second PH domain. TAPP1 and TAPP2 transcripts are expressed in a variety of tissues including lymphoid tissues. Using live-cell imaging, we demonstrate that TAPP1 and TAPP2 are recruited to the plasma membrane of BJAB human B-lymphoma cells upon activation through the B-cell antigen receptor (BCR). The C-terminal PH domain is necessary and sufficient for BCR-induced membrane recruitment of both TAPP1 and TAPP2. Blockade of phosphatidylinositol 3-kinase (PI3K) activity completely abolished BCR-induced recruitment of TAPP1 and TAPP2, while expression of active PI3K is sufficient to drive constitutive membrane localization of TAPP1 and TAPP2. TAPP1 and TAPP2 preferentially accumulate within ruffled, F-actin-rich areas of plasma membrane, suggesting a potential role in PI3K-driven cytoskeletal reorganization. Like Bam32, BCR-driven TAPP1 and TAPP2 recruitment is a relatively slow and sustained response, in contrast to Btk recruitment and Ca2+ mobilization responses, which are rapid and transient. Consistent with recent studies indicating that Bam32, TAPP1, and TAPP2 can bind to PI(3,4)P2, we find that membrane recruitment correlates well with production of PI(3,4)P2 but not with that of PI(3,4,5)P3. Our results indicate that TAPP1 and TAPP2 are direct targets of PI3K signaling that are recruited into plasma membranes with distinctive delayed kinetics and accumulate within F-actin-rich membrane ruffles. We postulate that the TAPPs function to orchestrate cellular responses during the sustained phase of signaling.
机译：我们报告了与Bam32相关的两个信号转导蛋白，称为TAPP1和TAPP2的表征。 Bam32，TAPP1和TAPP2具有几个特征，包括体积小（32至47 kDa），缺少酶结构域，人与小鼠之间的保守性高以及在其C末端附近存在pleckstrin同源（PH）结构域，其中包含3个-磷酸肌醇结合基序。与Bam32不同，TAPP1和TAPP2的N端区域包含第二个PH域。 TAPP1和TAPP2转录本在包括淋巴组织在内的多种组织中表达。使用活细胞成像，我们证明TAPP1和TAPP2被激活通过B细胞抗原受体（BCR）的BJAB人B淋巴瘤细胞的质膜。 C末端的PH结构域对于BCR诱导的TAPP1和TAPP2的膜募集是必要和充分的。磷脂酰肌醇3激酶（PI3K）活性的阻滞完全消除了BCR诱导的TAPP1和TAPP2的募集，而活性PI3K的表达足以驱动TAPP1和TAPP2的本构膜定位。 TAPP1和TAPP2优先积累在质膜富含F-肌动蛋白的褶皱区域内，表明在PI3K驱动的细胞骨架重组中可能发挥作用。与Bam32一样，BCR驱动的TAPP1和TAPP2募集反应相对缓慢且持续，而Btk募集和Ca 2 + 动员反应则是快速且短暂的。与最近的研究表明Bam32，TAPP1和TAPP2可以与PI（3,4）P 2 结合的研究一致，我们发现膜募集与PI（3,4）P 2 ，但不包含PI（3,4,5）P 3 。我们的结果表明，TAPP1和TAPP2是PI3K信号传导的直接靶标，这些信号被募集到具有独特延迟动力学的质膜中，并在富含F-肌动蛋白的膜皱褶中积累。我们假设TAPPs的功能是在信号持续阶段协调细胞反应。

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