Decreased intracellular degradation of insulin‐like growth factor binding protein‐3 in cathepsin L‐deficient fibroblasts

FEBS Letters

Kübler, Bernd⁴  Braulke, Thomas⁴  Peters, Christof²  Roth, Wera²  Saftig, Paul³  Zwad, Olaf⁴  Scharf, Jens-Gerd¹ 

[1]Department of Medicine, Division Gastroenterology and Endocrinology, University of Göttingen, D-37075 Göttingen, Germany

[2]Institute for Molecular Medicine and Cell Research, University of Freiburg, D-79106 Freiburg, Germany

[3]Institute of Biochemistry, University of Kiel, D-24098 Kiel, Germany

[4]Children's Hospital-Biochemistry, University of Hamburg, Martinistr. 52, D-20246 Hamburg, Germany

关键词: Insulin-like growth factor binding protein-3;    Cathepsin L;    Endocytosis;    IGF;    insulin-like growth factors;    IGFBP;    IGF binding protein;    CTSL;    cathepsin L;    DMEM;    Dulbecco's modified essential medium;    PAGE;    polyacrylamide gel electrophoresis;    PBS;    phosphate-buffered saline;   

DOI  :  10.1016/S0014-5793(01)03267-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown