Inhibition of constitutive signaling of Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor by protein kinases in mammalian cells in culture. Academic Article uri icon

Overview

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.

publication date

  • March 2, 1998

Research

keywords

  • Cyclic AMP-Dependent Protein Kinases
  • Herpesvirus 8, Human
  • Protein Kinase C
  • Protein Serine-Threonine Kinases
  • Receptor Protein-Tyrosine Kinases
  • Receptors, Chemokine
  • Sarcoma, Kaposi
  • Viral Proteins

Identity

PubMed Central ID

  • PMC2212177

Scopus Document Identifier

  • 0032473557

Digital Object Identifier (DOI)

  • 10.1084/jem.187.5.801

PubMed ID

  • 9480990

Additional Document Info

volume

  • 187

issue

  • 5