Cargando…

Osteoclasts express high levels of pp60c-src in association with intracellular membranes

Deletion of the c-src gene in transgenic mice by homologous recombination leads to osteopetrosis, a skeletal defect characterized by markedly deficient bone resorption (Soriano, P., C. Montgomery, R. Geske, and A. Bradley. 1991. Cell. 64:693-702), demonstrating a critical functional role of pp60c-sr...

Descripción completa

Detalles Bibliográficos
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1992
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2289690/
https://www.ncbi.nlm.nih.gov/pubmed/1385441
_version_ 1782152317948133376
collection PubMed
description Deletion of the c-src gene in transgenic mice by homologous recombination leads to osteopetrosis, a skeletal defect characterized by markedly deficient bone resorption (Soriano, P., C. Montgomery, R. Geske, and A. Bradley. 1991. Cell. 64:693-702), demonstrating a critical functional role of pp60c-src in osteoclast activity. Since decreased bone resorption could result from a defect either within the osteoclast or within other cells present in its environment, indirectly affecting osteoclast functions, we determined which cell(s) in bone expressed high levels of pp60c-src Measuring pp60c-src protein and kinase activities in osteoclasts and immunolocalizing pp60c-src in bone, we find that expression of pp60c-src is nearly as high in osteoclasts as in brain and platelets. In contrast, other bone cells contain only very low levels of the protein. In addition, expression of the c-src gene product increases when bone marrow cells are induced to express an osteoclast-like phenotype by 1,25-dihydroxy-vitamin D3, further suggesting that high expression of pp60c-src is part of the osteoclast phenotype. Three other src-like kinases, c-fyn, c-yes, and c- lyn, are also expressed in osteoclasts at ratios to pp60c-src similar to what is found in platelets. These src-related proteins do not, however, compensate for the absence of pp60c-src in the src- mice, thereby suggesting that pp60c-src may have a specific function in osteoclasts. Although further work is necessary to elucidate what the critical role of pp60c-src in osteoclasts is, our observation that the protein is associated mostly with the membranes of intracellular organelles suggests the possibility that this role might be at least in part related to the targeting or fusion of membrane vesicles.
format Text
id pubmed-2289690
institution National Center for Biotechnology Information
language English
publishDate 1992
publisher The Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-22896902008-05-01 Osteoclasts express high levels of pp60c-src in association with intracellular membranes J Cell Biol Articles Deletion of the c-src gene in transgenic mice by homologous recombination leads to osteopetrosis, a skeletal defect characterized by markedly deficient bone resorption (Soriano, P., C. Montgomery, R. Geske, and A. Bradley. 1991. Cell. 64:693-702), demonstrating a critical functional role of pp60c-src in osteoclast activity. Since decreased bone resorption could result from a defect either within the osteoclast or within other cells present in its environment, indirectly affecting osteoclast functions, we determined which cell(s) in bone expressed high levels of pp60c-src Measuring pp60c-src protein and kinase activities in osteoclasts and immunolocalizing pp60c-src in bone, we find that expression of pp60c-src is nearly as high in osteoclasts as in brain and platelets. In contrast, other bone cells contain only very low levels of the protein. In addition, expression of the c-src gene product increases when bone marrow cells are induced to express an osteoclast-like phenotype by 1,25-dihydroxy-vitamin D3, further suggesting that high expression of pp60c-src is part of the osteoclast phenotype. Three other src-like kinases, c-fyn, c-yes, and c- lyn, are also expressed in osteoclasts at ratios to pp60c-src similar to what is found in platelets. These src-related proteins do not, however, compensate for the absence of pp60c-src in the src- mice, thereby suggesting that pp60c-src may have a specific function in osteoclasts. Although further work is necessary to elucidate what the critical role of pp60c-src in osteoclasts is, our observation that the protein is associated mostly with the membranes of intracellular organelles suggests the possibility that this role might be at least in part related to the targeting or fusion of membrane vesicles. The Rockefeller University Press 1992-11-02 /pmc/articles/PMC2289690/ /pubmed/1385441 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Articles
Osteoclasts express high levels of pp60c-src in association with intracellular membranes
title Osteoclasts express high levels of pp60c-src in association with intracellular membranes
title_full Osteoclasts express high levels of pp60c-src in association with intracellular membranes
title_fullStr Osteoclasts express high levels of pp60c-src in association with intracellular membranes
title_full_unstemmed Osteoclasts express high levels of pp60c-src in association with intracellular membranes
title_short Osteoclasts express high levels of pp60c-src in association with intracellular membranes
title_sort osteoclasts express high levels of pp60c-src in association with intracellular membranes
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2289690/
https://www.ncbi.nlm.nih.gov/pubmed/1385441