title: Interleukin-1 modulates phosphorylation of proteins in human osteoblastic cells.
abstract: Interleukin-1 (IL-1) is a potent bone resorbing cytokine with diverse biological effects. We previously reported that IL-1 inhibits PDGF-AA-induced biological activities including PDGF-AA-induced tyrosyl phosphorylation. In the present studies, we first investigated and compared the tyrosyl phosphorylation pattern induced by EGF, IGF-1, PDGF-AA, and bFGF in human osteoblastic cells. We then examined the effect of IL-1 on the tyrosyl phosphoproteins induced by each ligand. Immunoblot analyses show that EGF, IGF-1, and PDGF-AA each elicit a different pattern of tyrosyl phosphorylated proteins in normal human osteoblastic cells. IL-1 beta inhibits PDGF-AA induced autophosphorylation by down-regulation of the PDGF-alpha receptor, as demonstrated by immunoprecipitation experiments. For other ligand-induced tyrosyl phosphoproteins, IL-1 beta reduced the intensity of EGF-induced pp55,000, and IGF-1 induced pp185,000 and pp175,000. These experiments indicate that IL-1 inhibits phosphorylation of specific proteins induced by growth factors. By using inhibitors of secondary message pathways, we determined that the inhibitory effect of IL-1 beta on PDGF-AA receptor binding and receptor tyrosyl autophosphorylation was not dependent on protein kinase A, protein kinase C, or the formation of prostaglandins. These data suggest the existence of an alternative pathway that may participate in IL-1 beta signaling.
authors.affiliation: Department of Oral Biology, Boston University School of Graduate Dentistry, Massachusetts, USA.
authors.forename: Y M
authors.initials: YM
authors.lastname: Kang
authors.forename: Y L
authors.initials: YL
authors.lastname: Yeh
authors.forename: D T
authors.initials: DT
authors.lastname: Graves
mesh_terms: D001859:Bone Neoplasms / Q000473:pathology; D001862:Bone Resorption / Q000139:chemically induced; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004591:Electrophoresis, Polyacrylamide Gel; D004815:Epidermal Growth Factor / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012516:Osteosarcoma / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000187:drug effects* / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D010982:Platelet-Derived Growth Factor; D011506:Proteins; D017978:Receptors, Growth Factor; C075278:platelet-derived growth factor A; D016222:Fibroblast Growth Factor 2; D014443:Tyrosine; D004815:Epidermal Growth Factor; D017479:Receptors, Platelet-Derived Growth Factor