Signaling by human herpesvirus 8 kaposin A through direct membrane recruitment of cytohesin-1

被引:87
作者
Kliche, S
Nagel, W
Kremmer, E
Atzler, C
Ege, A
Knorr, T
Koszinowski, U
Kolanus, W
Haas, J
机构
[1] Univ Munich, Max Von Pettenkofer Inst, Genzentrum, D-81377 Munich, Germany
[2] Univ Munich, Mol Biol Lab, Genzentrum, D-81377 Munich, Germany
[3] GSF Forschungszentrum Umwelt & Gesundheit GMBH, Inst Mol Immunol, D-81377 Munich, Germany
关键词
D O I
10.1016/S1097-2765(01)00227-1
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
The induction of a transformed cellular phenotype by viruses requires the modulation of signaling pathways through viral proteins. We show here that the phenotypic changes induced by the kaposin A protein of human herpesvirus 8 are mediated through its direct interaction with cytohesin-1, a guanine nucleotide exchange factor for ARF GTPases and regulator of integrin-mediated cell adhesion. Focus formation, stress fiber dissolution, and activation of the ERK-1/2 MAP kinase signal cascade were reverted by the cytohesin-1 E157K mutant, which is deficient in catalyzing guanine nucleotide exchange. Furthermore, liposome-embedded kaposin A specifically stimulates cytohesin-1 dependent GTP binding of myristoylated ARF1 in vitro. These results suggest a previously unknown involvement of ARF GTPases in the control of cellular functions by herpesviruses.
引用
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页码:833 / 843
页数:11
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