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首页> 外文期刊>Journal of Cellular Physiology >The N-terminus of phosphoinositide 3-kinase-C2beta regulates lipid kinase activity and binding to clathrin.
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The N-terminus of phosphoinositide 3-kinase-C2beta regulates lipid kinase activity and binding to clathrin.

机译：磷酸肌醇分子的n端3-kinase-C2beta调节脂质激酶活性和绑定网格蛋白。

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摘要

The class II phosphoinositide 3-kinase (PI3K)-C2beta is recruited to polypeptide growth factor receptors following ligand stimulation. In contrast to the class I A p85/p110 heterodimers, this interaction is dependent upon proline residues present within the N-terminal sequence of the 3-phosphoinositide kinase. However, the mechanism by which PI3K-C2beta catalytic activity is regulated currently remains unknown. In many tumours, increased expression of ErbB receptors confers a poor prognosis. We demonstrate that increased expression of EGFR enhanced its association with PI3K-C2beta following stimulation with EGF. Deletion of the first proline rich region within the N-terminus precluded recruitment of PI3K-C2beta to activated EGFR. Although deletion of the first proline rich motif also rendered the enzyme catalytically inactive, further deletions (residues 1-148 and 1-261) that removed the second and third proline rich motifs increased kinase activity. These data confirm a regulatory role for the N-terminus of class II PI3K enzymes suggesting that catalytic activity is regulated by factors that associate with this region during recruitment to activated growth factor receptors. Using an N-terminal PI3K-C2beta-GST fusion protein, clathrin heavy chain was affinity purified from A431 cell lysates. Association of PI3K-C2beta with clathrin was confirmed by co-immunoprecipitation from cell lysates while intracellular co-localisation of PI3K-C2beta and clathrin was confirmed by confocal microscopy. Our findings demonstrate for the first time that the PI3K-C2beta isoform associates with clathrin and thus provides a link between receptor mediated intracellular signalling and clathrin coated vesicle transport.
机译：类二磷酸肌醇3-kinase(PI3K) -C2beta招募多肽生长因子受体配体刺激。对比类我p85 / p110形成,这种交互是依赖于脯氨酸残留在n端序列3-phosphoinositide激酶。PI3K-C2beta催化活性的机制目前监管仍然是未知的。肿瘤,增加ErbB受体的表达授予预后不良。表皮生长因子受体表达增加增强它与PI3K-C2beta后与EGF刺激。n端内的脯氨酸丰富的地区杜绝招聘PI3K-C2beta激活表皮生长因子受体。主题也呈现了酶催化地不活跃,进一步删除(残留1 - 148和1 - 261),第二个和第三个脯氨酸丰富的图案激酶活性增加。确认的n端监管作用二类PI3K酶表明催化活动是由关联的因素与这一地区招聘期间激活生长因子受体。PI3K-C2beta-GST融合蛋白,网格蛋白重链从A431细胞亲和纯化溶菌产物。证实了从细胞co-immunoprecipitation吗溶菌产物在细胞内co-localisation证实了PI3K-C2beta和网格蛋白共焦显微镜。第一次PI3K-C2beta同种型同事与网格蛋白,从而提供了一个链接之间受体介导的细胞内信号和网格蛋白有被小泡运输。

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