Signaling by human herpesvirus 8 kaposin A through direct membrane recruitment of cytohesin-1.
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.
Kliche
S
S
Max-von-Pettenkofer Institut, LMU München, 81377 Münich, Germany.
Nagel
W
W
Kremmer
E
E
Atzler
C
C
Ege
A
A
Knorr
T
T
Koszinowski
U
U
Kolanus
W
W
Haas
J
J
D016475:3T3 Cells; D020823:ADP-Ribosylation Factor 1 / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002472:Cell Transformation, Viral / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D020662:Guanine Nucleotide Exchange Factors; D019288:Herpesvirus 8, Human; D006801:Humans; D019169:Jurkat Cells; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D008969:Molecular Sequence Data; D010641:Phenotype; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D020662:Guanine Nucleotide Exchange Factors; D008565:Membrane Proteins; D014764:Viral Proteins; C100723:cytohesin-1; C120136:kaposin B protein, Human herpesvirus 8; D019950:Mitogen-Activated Protein Kinase 1; D020823:ADP-Ribosylation Factor 1