Identification of a novel function of the clathrin-coated structure at the plasma membrane in facilitating GM-CSF receptor-mediated activation of JAK2

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题名:	Identification of a novel function of the clathrin-coated structure at the plasma membrane in facilitating GM-CSF receptor-mediated activation of JAK2
作者:	簡汎清;Chen, Ping-Hung;Chien, Fan-Ching;Lee, Sue-Ping;Chan, Woan-Eng;Lin, I-Hsuan;Liu, Chun-Shan;Lee, Fang-Jen;Lai, Jiann-Shiun;Chen, Peilin;yang-yen, Hsin-Fang;Yen, Jeffrey
贡献者:	理學院光電科學與工程學系
关键词:	Adaptor Proteins, Vesicular Transport - metabolism;Amino Acid Motifs;Amino Acid Sequence;Animals;Binding;Biology;Bioscience;Calcium;Cancer;casein kinase 2;Cell;Clathrin - metabolism;clathrin-coated pit;Coated Pits, Cell-Membrane - metabolism;Cycle;Endocytosis;Enzyme Activation;GM-CSF receptor;HeLa Cells;Humans;Jak2;Janus Kinase 2 - metabolism;Landes;Ligands;Mice;Models, Biological;Molecular Sequence Data;Mutant Proteins - metabolism;Mutation - genetics;myeloproliferative disorders;Organogenesis;Protein Binding;Protein Conformation;Protein Transport;Proteins;Receptors, Granulocyte-Macrophage Colony-Stimulating Factor - chemistry;Receptors, Granulocyte-Macrophage Colony-Stimulating Factor - metabolism;Signal Transduction
日期:	2012-10-01
上传时间:	2026-04-23 11:33:00 (UTC+8)
出版者:	Landes Bioscience;United States: Taylor & Francis
摘要:	摘要： It is well known that ligand binding to the high-affinity GM-CSF receptor (GMR) activates JAK2. However, how and where this event occurs in a cellular environment remains unclear. Here, we demonstrate that clathrin- but not lipid raft-mediated endocytosis is crucial for GMR signaling. Knockdown expression of clathrin heavy chain or intersectin 2 (ITSN2) attenuated GMR-mediated activation of JAK2, whereas inhibiting clathrin-coated pits or plagues to bud off the membrane by the dominant-negative mutant of dynamin enhanced such event. Moreover, unlike the wild-type receptor, an ITSN2-non-binding mutant of GMR defective in targeting to clathrin-coated pits or plagues [collectively referred to as clathrin-coated structures (CCSs) here] failed to activate JAK2 at such locations. Additional experiments demonstrate that ligand treatment not only enhanced JAK2/GMR association at CCSs, but also induced a conformational change of JAK2 which is required for JAK2 to be activated by CCS-localized CK2. Interestingly, ligand-independent activation of the oncogenic mutant of JAK2 (JAK2V617F) also requires the targeting of this mutant to CCSs. But JAK2V617F seems to be constitutively in an open conformation for CK2 activation. Together, this study reveals a novel functional role of CCSs in GMR signaling and the oncogenesis of JAK2V617F. 其他題名： Cell Cycle 出版者： United States: Taylor & Francis 出版日期： 2012-10-01 出處： Cell cycle (Georgetown, Tex.), 2012-10, Vol.11 (19), p.3611-3626 資源來源： Taylor & Francis Journals 版權： Copyright © 2012 Landes Bioscience 2012 識別號： ISSN: 1538-4101 識別號： ISSN: 1551-4005 識別號： EISSN: 1551-4005 識別號： DOI: 10.4161/cc.21920 識別號： PMID: 22935703
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