Abstract
Proteolysis of insulin-like growth factor binding proteins (IGFBPs) is the major mechanism of releasing IGFs from their IGFBP complexes. Analysis of fibroblasts deficient for the lysosomal cysteine protease cathepsin L (CTSL) revealed an accumulation of IGFBP-3 in the medium which was due neither to alterations in IGFBP-3 mRNA expression nor to extracellular IGFBP-3 protease activity. Incubation of CTSL-deficient fibroblasts with radiolabeled IGFBP-3 followed by subcellular fractionation indicates that both intact and fragmented IGFBP-3 accumulate transiently in endosomal and lysosomal fractions of CTSL-deficient cells. This suggests the involvement of CTSL in the intracellular degradation of IGFBP-3 representing a new mechanism to regulate the extracellular concentration of IGFBP-3.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cathepsin L
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Cathepsins / deficiency*
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Cathepsins / genetics
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Cathepsins / metabolism*
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Cells, Cultured
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Culture Media, Conditioned / chemistry
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Culture Media, Conditioned / metabolism
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Cysteine Endopeptidases
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Endocytosis
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Endosomes / chemistry
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Extracellular Space / metabolism
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Fibroblasts / cytology
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Fibroblasts / metabolism*
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Insulin-Like Growth Factor Binding Protein 3 / chemistry
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Insulin-Like Growth Factor Binding Protein 3 / genetics
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Insulin-Like Growth Factor Binding Protein 3 / metabolism*
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Insulin-Like Growth Factor Binding Protein 4 / chemistry
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Insulin-Like Growth Factor Binding Protein 4 / genetics
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Insulin-Like Growth Factor Binding Protein 4 / metabolism
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Intracellular Fluid / metabolism*
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Lysosomes / chemistry
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Mice
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Mice, Knockout
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RNA, Messenger / biosynthesis
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Subcellular Fractions / chemistry
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Substrate Specificity
Substances
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Culture Media, Conditioned
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Insulin-Like Growth Factor Binding Protein 3
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Insulin-Like Growth Factor Binding Protein 4
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RNA, Messenger
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Cathepsins
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Cysteine Endopeptidases
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Cathepsin L
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Ctsl protein, mouse