ACAP4 Protein Cooperates with Grb2 Protein to Orchestrate Epidermal Growth Factor-stimulated Integrin β1 Recycling in Cell Migration

被引:17
作者
Yu, Xue [1 ]
Wang, Fengsong [1 ,2 ]
Liu, Hongsheng [1 ]
Adams, Gregory [2 ]
Aikhionbare, Felix [2 ]
Liu, Dong [3 ]
Cao, Xinwang [1 ,4 ]
Fan, Libin [4 ]
Hu, Guohong [5 ]
Chen, Yong [3 ]
Frost, Andra [6 ]
Partridge, Edward [6 ]
Ding, Xia [7 ]
Yao, Xuebiao [1 ,2 ]
机构
[1] Univ Sci & Technol China, Anhui Key Lab Cellular Dynam, Hefei 230027, Peoples R China
[2] Morehouse Sch Med, Dept Physiol, Atlanta, GA 30310 USA
[3] Xijing Hosp, Dept Hepatobiliary Surg, Xian 710032, Peoples R China
[4] Anhui Med Univ, Sch Life Sci, Hefei 230027, Peoples R China
[5] SIBS SJTU Inst Hlth Sci, Key Lab Stem Cell Biol, Shanghai 200025, Peoples R China
[6] Univ Alabama, Sch Med, Ctr Comprehens Canc, Birmingham, AL 35294 USA
[7] Beijing Univ Chinese Med, Sch Grad Studies, Beijing 100029, Peoples R China
基金
美国国家卫生研究院;
关键词
GUANINE-NUCLEOTIDE EXCHANGE; RECEPTOR TYROSINE KINASES; ENDOCYTIC TRANSPORT; SIGNAL-TRANSDUCTION; BREAST-CANCER; RHOA ACTIVITY; SH3; DOMAINS; RAS PATHWAY; ADHESION; ARF6;
D O I
10.1074/jbc.M111.278770
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
ARF6 GTPase is an important regulator of membrane trafficking and actin-based cytoskeleton dynamics active at the leading edge of migrating cells. The integrin family heterodimeric transmembrane proteins serve as major receptors for extracellular matrix proteins, which play essential roles in cell adhesion and migration. Our recent proteomic analyses of ARF6 effectors have identified a novel ARF6 GTPase-activating protein, ACAP4, essential for EGF-induced cell migration. However, molecular mechanisms underlying ACAP4-mediated cell migration have remained elusive. Here, we show that ACAP4 regulates integrin beta 1 dynamics during EGF-stimulated cell migration by interaction with Grb2. Our biochemical study shows that EGF stimulation induces phosphorylation of tyrosine 733, which enables ACAP4 to bind Grb2. This interaction of ACAP4 with Grb2 regulates integrin beta 1 recycling to the plasma membrane. Importantly, knockdown of ACAP4 by siRNA or overexpression of ACAP4 decreased recycling of integrin beta 1 to the plasma membrane and reduced integrin-mediated cell migration. Taken together, these results suggest a novel function for ACAP4 in the regulation cell migration through controlling integrin beta 1 dynamics.
引用
收藏
页码:43735 / 43747
页数:13
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