A Novel AAK1 Splice Variant Functions at Multiple Steps of the Endocytic Pathway

Davin M. Henderson; Sean D. Conner

首页> 外文期刊>Molecular biology of the cell >A Novel AAK1 Splice Variant Functions at Multiple Steps of the Endocytic Pathway

【24h】

A Novel AAK1 Splice Variant Functions at Multiple Steps of the Endocytic Pathway

机译：内吞途径的多个步骤的新型AAK1剪接变异函数。

获取原文

掌桥外文数据库（机构版） >>

开具论文收录证明 >>

文献代查 >>

页面导航

摘要
著录项
相似文献
相关主题

摘要

Phosphorylation is a critical step in regulating receptor transport through the endocytic pathway. AAK1 is a serine/threonine kinase that is thought to coordinate the recruitment of AP-2 to receptors containing tyrosine-based internalization motifs by phosphorylating the μ2 subunit. Here we have identified a long form of AAK1 (AAK1L) that contains an extended C-terminus that encodes an additional clathrin-binding domain (CBD2) consisting of multiple low-affinity interaction motifs. Protein interaction studies demonstrate that AAK1L CBD2 directly binds clathrin. However, in vitro kinase assays reveal little difference between AAK1 isoforms in their basal or clathrin-stimulated kinase activity toward the AP-2 μ2 subunit. However, overexpression of AAK1L CBD2 impairs transferrin endocytosis, confirming an endocytic role for AAK1. Surprisingly, CBD2 overexpression or AAK1 depletion by RNA interference significantly impairs transferrin recycling from the early/sorting endosome. These observations suggest that AAK1 functions at multiple steps of the endosomal pathway by regulating transferrin internalization and its rapid recycling back to the plasma membrane from early/sorting endosome.

机译：磷酸化是调节受体通过内吞途径的关键步骤。 AAK1是一种丝氨酸/苏氨酸激酶，被认为通过将μ2亚基磷酸化来协调AP-2募集到含有基于酪氨酸的内在基序的受体。在这里，我们确定了一种长形式的AAK1（AAK1L），其中包含一个扩展的C端，该C端编码一个由多个低亲和力相互作用基序组成的附加网格蛋白结合域（CBD2）。蛋白质相互作用研究表明，AAK1L CBD2直接结合网格蛋白。但是，体外激酶测定显示，AAK1亚型之间的基础或网格蛋白刺激的针对AP-2μ2亚基的激酶活性之间几乎没有差异。但是，AAK1L CBD2的过表达损害转铁蛋白的内吞作用，从而确认AAK1的内吞作用。出人意料的是，RNA干扰引起的CBD2过表达或AAK1耗竭显着削弱了早期/分选内体中转铁蛋白的回收利用。这些观察结果表明，AAK1通过调节转铁蛋白内在化及其从早期/分选的内体快速循环回质膜的功能，在内体途径的多个步骤中发挥作用。

著录项

来源
《Molecular biology of the cell》 |2007年第7期|共9页
作者
Davin M. Henderson; Sean D. Conner;
展开▼
作者单位

展开▼
收录信息
原文格式 PDF
正文语种
中图分类分子生物学;
关键词

相似文献

外文文献
中文文献
专利

1. A novel AAK1 splice variant functions at multiple steps of the endocytic Pathway [J] . Henderson DM, Conner SD Molecular biology of the cell . 2007,第7期

机译：新型AAK1剪接变体在胞吞途径的多个步骤中起作用
2. Distinct Contributions of Enzymic Functional Groups to the 2′,3′-Cyclic Phosphodiesterase, 3′-Phosphate Guanylylation, and 3′-ppG/5′-OH Ligation Steps of the Escherichia coli RtcB Nucleic Acid Splicing Pathway [J] . William P. Maughan, Stewart Shuman Journal of bacteriology . 2016,第8期

机译：酶功能基团对大肠杆菌RtcB核酸剪接途径的2'，3'-环磷酸二酯酶，3'-磷酸鸟苷酸化和3'-ppG / 5'-OH连接步骤的不同贡献
3. Distinct Contributions of Enzymic Functional Groups to the 2′,3′-Cyclic Phosphodiesterase, 3′-Phosphate Guanylylation, and 3′-ppG/5′-OH Ligation Steps of the Escherichia coli RtcB Nucleic Acid Splicing Pathway [J] . William P. Maughan, Stewart Shuman Journal of bacteriology . 2016,第8期

机译：酶功能基团对大肠杆菌RtcB核酸剪接途径的2'，3'-环磷酸二酯酶，3'-磷酸鸟苷酸化和3'-ppG / 5'-OH连接步骤的不同贡献
4. Functional Splice Variants of the Type II G Protein—Coupled Receptor (VPAC2) for Vasoactive Intestinal Peptide in Mouse and Human Lymphocytes [C] . ALLISON L. MILLER, DEEPTI VERMA, CAROLA GRINNINGER, International Symposium on VIP, PACAP, and Related Peptides . 2006

机译：II型G蛋白偶联受体（VPAC2）的功能性接头变体用于小鼠和人淋巴细胞中的血管活性肠肽
5. HyPR-MS for Multiplexed and Splice Variant-Specific Discovery of RNA-Protein Interactomes [D] . Knoener, Rachel A. 2017

机译：HyPR-MS用于RNA-蛋白质相互作用组的多重和剪接变体特异性发现。
6. A Novel AAK1 Splice Variant Functions at Multiple Steps of the Endocytic Pathway [O] . Davin M. Henderson, Sean D. Conner 2007

机译：内吞途径的多个步骤的新型AAK1剪接变异函数。
7. A Novel AAK1 Splice Variant Functions at Multiple Steps of the Endocytic Pathway [O] . Henderson, Davin M., Conner, Sean D. 2007

机译：内吞途径的多个步骤的新型AAK1剪接变异函数。

A Novel AAK1 Splice Variant Functions at Multiple Steps of the Endocytic Pathway

摘要

著录项

相似文献

相关主题

期刊订阅