Decreased intracellular degradation of insulin-like growth factor binding protein-3 in cathepsin L-deficient fibroblasts.
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.
Zwad
Olaf
O
Cildren's Hospital-Biochemistry, University of Hamburg, Germany.
Kübler
Bernd
B
Roth
Wera
W
Scharf
Jens-Gerd
JG
Saftig
Paul
P
Peters
Christof
C
Braulke
Thomas
T
D000818:Animals; D056668:Cathepsin L; D002403:Cathepsins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000378:metabolism; D003546:Cysteine Endopeptidases; D004705:Endocytosis; D011992:Endosomes / Q000737:chemistry; D005110:Extracellular Space / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D007424:Intracellular Fluid / Q000378:metabolism*; D008247:Lysosomes / Q000737:chemistry; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis; D013347:Subcellular Fractions / Q000737:chemistry; D013379:Substrate Specificity
D017077:Culture Media, Conditioned; D018972:Insulin-Like Growth Factor Binding Protein 3; D018974:Insulin-Like Growth Factor Binding Protein 4; D012333:RNA, Messenger; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D056668:Cathepsin L; C534278:Ctsl protein, mouse