Structure-function analysis reveals discrete β3 integrin inside-out and outside-in signaling pathways in platelets

Author:

Zou Zhiying1,Chen Hong1,Schmaier Alec A.1,Hynes Richard O.2,Kahn Mark L.1

Affiliation:

1. Division of Cardiology and Department of Medicine, University of Pennsylvania, Philadelphia;

2. Center for Cancer Research, Massachusetts Institute of Technology, Cambridge

Abstract

Abstract A unique aspect of integrin receptor function is the transmission of bidirectional signals. In platelets αIIbβ3 integrins require “inside-out” signals to bind fibrinogen and form thrombi. Following ligand binding, αIIbβ3 integrins generate “outside-in” signals that contribute to thrombus stability. Because integrin cytoplasmic tails are short and lack enzymatic activity, bidirectional signals are believed to be mediated by interactions with intracellular proteins, but the molecular basis for integrin signal transduction remains poorly understood. In the present study we have used retroviral vectors to express αIIbβ3 integrins with mutant β3 tails in mouse platelets and test mechanisms of bidirectional signaling. Using this approach we identify mutations (eg, β3Y747A) that confer loss of signaling in both directions and others (eg, β3T762A) that confer a selective loss of outside-in signals. These results reveal the presence of discrete bidirectional signaling pathways controlled by integrin β subunits in platelets and describe a high-throughput means of further investigating these pathways in vivo.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3