Reduced G-protein-coupled-receptor kinase 2 activity results in impairment of osteoblast function
| Autor: | Michael Bliziotes, Kristine M. Wiren, X.-W. Zhang, Robert A. Nissenson, M Gunness |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Histology
Physiology Endocrinology Diabetes and Metabolism MAPK7 Receptors Cell Surface Mitogen-activated protein kinase kinase Biology Cell Line MAP2K7 GTP-Binding Proteins Animals ASK1 Insulin-Like Growth Factor I Phosphorylation MAPK14 Osteoblasts Epidermal Growth Factor MAP kinase kinase kinase Cyclic AMP-Dependent Protein Kinases Rats Cell biology Enzyme Activation Biochemistry beta-Adrenergic Receptor Kinases Mutation biology.protein Tetradecanoylphorbol Acetate Cyclin-dependent kinase 9 Mitogen-Activated Protein Kinases Cell Division Platelet-derived growth factor receptor |
| Zdroj: | Bone. 27:367-373 |
| ISSN: | 8756-3282 |
| DOI: | 10.1016/s8756-3282(00)00338-0 |
| Popis: | 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, beta-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. |
| Databáze: | OpenAIRE |
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