Roles of scaffolding protein Gab1 in regulation of myeloid dendritic cell-mediated allergic asthma
作者单位：zhejang University Zhejang University
会议名称：《中国生物化学与分子生物学会第十一次会员代表大会暨201...》
会议日期：2014年
学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 1001[医学-基础医学(可授医学、理学学位)] 07[理学] 10[医学]
关 键 词：Gab1 dendritic cell allergic asthma
摘 要：Scaffolding proteins Gab1 is ubiquitously expressed and belongs to the GAB family(GABs),which integrates multiple signal events.This protein family has recently attracted interestthat genetic variants of human GAB1 are considered a risk factor for asthma.Our previousresearch has revealed a novel function of Gab2 in mediating mucin gene expression andGoblet cell hyperplasia(GCH),which is an important process in asthma.However,the functionof Gab1 in asthma remains unclear.In asthma exacerbated patients,we found a prominentelevated level of Gab1 in peripheral blood monouclear cells compared to that of convalescencepatients.Next,we generated conditional Gab1 deletion mice in myeloid cells(Gab1 KO mice)to determinate physiological the role of Gab1 in asthma.Lung histologyand mucus metaplasia indicated that disruption of Gab1 in dendritic cells(DCs)leads to alleviatedasthmatic inflammation.Future investigation showed that loss of Gab1results inimpaired DC migration to lymph node,while has no influences on DC maturation、antigenuptake and presentation.Mechanically,Gab1 is essentially involved in CCL19-mediatedAKT activation.Together,these finding has characterized a novel of Gab1 in mediating DCmigration and that deregulation of Gab1 signal in lungs predisposes asthmatic inflammation.