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, Carlos Bais, Ethel Cesarman, Enrique A. Mesri, Marvin C. Gershengorn

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)801-806
Number of pages6
JournalJournal of Experimental Medicine
Volume187
Issue number5
DOIs
StatePublished - Mar 2 1998

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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