Reduced G-protein-coupled-receptor kinase 2 activity results in impairment of osteoblast function

M. Bliziotes, M. Gunness, X. W. Zhang, R. Nissenson, Kristine Wiren

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Rapid phosphorylation of many G-protein-coupled receptors (GPCRs) by G- protein-coupled receptor kinases (GRKs) accompanies stimulus-driven desensitization. Recent evidence suggests that GRKs and their associated arresting proteins, β-arrestins, function as essential elements in the GPCR- mediated mitogen-activated protein (MAP) kinase signaling cascade. We investigated the interaction between GRKs and MAP kinase activation by growth factors in UMR 106-H5 osteoblastic cells stably expressing a dominant negative mutant of GRK2 (K220R). Expression of K220R in osteoblastic cells results in reduced cellular proliferation, both basally and in response to insulin-like growth factor-1 (IGF-1), and blunting of IGF-1- and EGF-induced MAP kinase activation. Reduced MAP kinase activation is not associated with alterations in IGF-1-receptor autophosphorylation. Both a constitutively active Ras mutant and PMA fully activate MAP kinase in K220R cells. We found that disruption of the GRK2 gene results in: (1) reduced osteoblast proliferation in response to growth factors, and (2) impaired receptor tyrosine kinase activation of mitogenic signaling pathways. Thus, GRK2 may regulate growth factor responsiveness in osteoblasts by modulating multiprotein complex formation following receptor tyrosine kinase activation. (C) 2000 by Elsevier Science Inc.

Original languageEnglish (US)
Pages (from-to)367-373
Number of pages7
JournalBone
Volume27
Issue number3
DOIs
StatePublished - Sep 2000

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G-Protein-Coupled Receptor Kinase 2
Mitogen-Activated Protein Kinases
Osteoblasts
G-Protein-Coupled Receptor Kinases
Intercellular Signaling Peptides and Proteins
Receptor Protein-Tyrosine Kinases
Somatomedins
G-Protein-Coupled Receptors
Arrestins
Somatomedin Receptors
Multiprotein Complexes
Epidermal Growth Factor
Phosphorylation
Cell Proliferation
Genes
Proteins

Keywords

  • Bone
  • Desensitization
  • G protein
  • Growth factors
  • Mitogen-activated (MAP) kinase
  • Receptor protein tyrosine kinase

ASJC Scopus subject areas

  • Physiology
  • Hematology

Cite this

Reduced G-protein-coupled-receptor kinase 2 activity results in impairment of osteoblast function. / Bliziotes, M.; Gunness, M.; Zhang, X. W.; Nissenson, R.; Wiren, Kristine.

In: Bone, Vol. 27, No. 3, 09.2000, p. 367-373.

Research output: Contribution to journalArticle

Bliziotes, M. ; Gunness, M. ; Zhang, X. W. ; Nissenson, R. ; Wiren, Kristine. / Reduced G-protein-coupled-receptor kinase 2 activity results in impairment of osteoblast function. In: Bone. 2000 ; Vol. 27, No. 3. pp. 367-373.
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