The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/3/801/ $5.00
The Journal of Experimental Medicine, Volume 187, Number 5, March 2, 1998 801-806

Brief Definitive Reports

Inhibition of Constitutive Signaling of Kaposi's Sarcoma–associated Herpesvirus G Protein–Coupled Receptor by Protein Kinases in Mammalian Cells in Culture

Elizabeth Geras-Raaka*, Leandros Arvanitakis{ddagger}, Carlos Bais§, Ethel Cesarman{ddagger}, Enrique A. Mesri§, and Marvin C. Gershengorn*

From the * Division of Molecular Medicine, the Department of Medicine, the {ddagger} Department of Pathology, and the § Division of Hematology-Oncology, the Department of Medicine, Cornell University Medical College, New York 10021

Kaposi's sarcoma–associated herpesvirus (KSHV)/human herpesvirus 8, which is consistently present in tissues of patients with Kaposi's sarcoma and primary effusion lymphomas, contains a gene that encodes a G protein–coupled receptor (KSHV-GPCR). We recently showed that KSHV-GPCR exhibits constitutive signaling via activation of phosphoinositide-specific phospholipase C and stimulates cell proliferation and transformation. In this study, we determined whether normal cellular mechanisms could inhibit constitutive signaling by KSHV-GPCR and thereby KSHV-GPCR–stimulated proliferation. We show that coexpression of GPCR-specific kinases (GRKs) and activation of protein kinase C inhibit constitutive signaling by KSHV-GPCR in COS-1 monkey kidney cells and in mouse NIH 3T3 cells. Moreover, GRK-5 but not GRK-2 inhibits KSHV-GPCR–stimulated proliferation of rodent fibroblasts. These data provide evidence that cell regulatory pathways of receptor desensitization may be therapeutic targets in human diseases involving constitutively active receptors.

We thank Bianca Santomasso for excellent technical assistance.

This work was supported by National Institutes of Health grants DK-43036 (to M.C. Gershengorn), CA-73531 (to E. Cesarman) and AI-39192 (to E.A. Mesri).

Address correspondence to Marvin C. Gershengorn, Cornell University Medical College, 1300 York Ave., Rm A328, New York, NY 10021. Phone: 212-746-6275; Fax: 212-746-6289; E-mail: mcgersh{at}mail.med.cornell.edu


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