Caveolin-enriched membrane signaling complexes in human and murine osteoblasts

Osteoblasts receive regulatory signals from hormones, growth factors, calci um, extracellular matrix, and other cells through a variety of receptors th at utilize an array of signaling pathways and cytoplasmic messengers. This article addresses the nonuniform distribution of important signaling molecu les (platelet-derived growth factor receptors [PDGFRs], nonreceptor tyrosin e kinases, tyrosine kinase adaptor proteins, G proteins, and nitric oxide s ynthases [NOSs]) in the surface membranes of human and murine osteoblasts, We show that particular inner leaflet signaling molecules (e.g., heterotrim eric G proteins and Sre family tyrosine kinases) are clustered and concentr ated in Triton X-100-insoluble membranes that are enriched in caveolin, the major structural component of caveolae (50- to 100-nm flask-shaped invagin ations 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 effec ters are present in the caveolin-enriched membrane fraction of osteoblasts.