共 49 条
GEP100/BRAG2:: Activator of ADP-ribosylation factor 6 for regulation of cell adhesion and actin cytoskeleton via E-cadherin and α-catenin
被引:59
作者:
Hiroi, Toyoko
[1
]
Someya, Akimasa
[1
]
Thompson, Walter
[1
]
Moss, Joel
[1
]
Vaughan, Martha
[1
]
机构:
[1] NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA
来源:
关键词:
adherens junction;
F-actin;
D O I:
10.1073/pnas.0604091103
中图分类号:
O [数理科学和化学];
P [天文学、地球科学];
Q [生物科学];
N [自然科学总论];
学科分类号:
07 ;
0710 ;
09 ;
摘要:
GEP(100) (p100) was identified as an ADP-ribosylation factor (ARF) guanine nucleotide-exchange protein (GEP) that partially colocalized with ARF6 in the cell periphery. p100 preferentially accelerated guanosine 5[gamma-thio]triphosphate (GTP gamma S) binding by ARF6, which participates in protein trafficking near the plasma membrane, including receptor recycling, cell adhesion, and cell migration. Here we report that yeast two-hybrid screening of a human fetal brain cDNA library using p100 as bait revealed specific interaction with alpha-catenin, which is known as a regulator of adherens junctions and actin cytoskeleton remodeling. Interaction of p100 with alpha-catenin was confirmed by coimmunoprecipitation of the endogenous proteins from human HepG2 or CaSki cells, although colocalization was difficult to demonstrate microscopically. alpha-Catenin enhanced GTP gamma S binding by ARF6 in vitro in the presence of p100. Depletion of p100 by small interfering RNA (siRNA) treatment in HepG2 cells resulted in E-cadherin content 3-fold that in control cells and blocked hepatocyte growth factor-induced redistribution of E-cadherin, consistent with a known role of ARF6 in this process. F-actin was markedly decreased in normal rat kidney (NRK) cells overexpressing wild-type p100, but not its GEP-inactive mutants, also consistent with the conclusion that p100 has an important role in the activation of ARF6 for its functions in both E-cadherin recycling and actin remodeling.
引用
收藏
页码:10672 / 10677
页数:6
相关论文