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Keywords:

  • osteoblast;
  • caveolae;
  • caveolin;
  • platelet-derived growth factor;
  • signaling

Abstract

Osteoblasts receive regulatory signals from hormones, growth factors, calcium, extracellular matrix, and other cells through a variety of receptors that utilize an array of signaling pathways and cytoplasmic messengers. This article addresses the nonuniform distribution of important signaling molecules (platelet-derived growth factor receptors [PDGFRs], nonreceptor tyrosine kinases, tyrosine kinase adaptor proteins, G proteins, and nitric oxide synthases [NOSs]) in the surface membranes of human and murine osteoblasts. We show that particular inner leaflet signaling molecules (e.g., heterotrimeric G proteins and Src family tyrosine kinases) are clustered and concentrated in Triton X-100-insoluble membranes that are enriched in caveolin, the major structural component of caveolae (50- to 100-nm flask-shaped invaginations of the plasma membrane that apparently are organized by oligomers of the protein caveolin). In addition, we show that a subset of highly ligand-responsive PDGFRs and mitogen-activated protein (MAP) kinase pathway effectors are present in the caveolin-enriched membrane fraction of osteoblasts.