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

S Kliche, W Nagel, E Kremmer, C Atzler, A Ege, T Knorr, U Koszinowski, W Kolanus, J Haas

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)833-843
Number of pages11
JournalMolecular Cell
Volume7
Issue number4
Publication statusPublished - Apr 2001

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