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Mol Cell. 2001 Apr;7(4):833-43.

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

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1
Max-von-Pettenkofer Institut, LMU München, 81377 Münich, Germany.

Abstract

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.

PMID:
11336706
DOI:
10.1016/s1097-2765(01)00227-1
[Indexed for MEDLINE]
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