scholarly journals Developmental Regulation of the Soluble Form of Insulin-Like Growth Factor-II/Mannose 6-Phosphate Receptor in Human Serum and Amniotic Fluid1

1998 ◽  
Vol 83 (2) ◽  
pp. 437-442 ◽  
Author(s):  
Y. Xu ◽  
A. Papageorgiou ◽  
C. Polychronakos
1988 ◽  
Vol 252 (3) ◽  
pp. 795-799 ◽  
Author(s):  
C Causin ◽  
A Waheed ◽  
T Braulke ◽  
U Junghans ◽  
P Maly ◽  
...  

Human serum and urine contain polypeptides which bind mannose 6-phosphate (M6P) and insulin-like growth factor II (IGF II) and crossreact with antibodies against the M6P/IGF II receptor. These polypeptides are considered to be fragments of the M6P/IGF II receptor. The major Mr approx. 205,000 fragment in serum and urine is about 10 kDa smaller in size than the membrane-associated receptor and is accompanied by minor forms with Mr values ranging from 104,000 to 180,000. The presence of receptor fragments in biological fluids indicates that shedding is one of the mechanisms contributing to the turnover of the M6P/IGF II receptor and that receptor fragments are part of the heterogenous group of serum proteins whic bind IGF II.


2001 ◽  
Vol 79 (4) ◽  
pp. 469-477
Author(s):  
Khadija Tahiri ◽  
Laurence Cam ◽  
Bernard Desbuquois ◽  
Geneviève Chauvet

A truncated, soluble form of the insulin-like growth factor-II–mannose 6-phosphate (IGF-II–M6P) receptor has been identified in serum and shown to be released from cultured tissues and cells, liver being the main contributor to serum receptor in adult rats. In the present study, the processing of the IGF-II–M6P receptor has been characterized in isolated liver subcellular fractions using ligand binding, affinity crosslinking, and Western immunoblotting techniques. The receptor in plasma membrane fractions differed from that in Golgi-endosomal fractions by: (i) a lower molecular size upon reducing polyacrylamide gel electrophoresis (245 vs. 255 kDa); (ii) a less tight membrane association as judged upon extractibility by NaCl; and (iii) the inability to recognize antibody anti-22C, directed against the cytoplasmic domain of the receptor. Incubation of cell fractions at 30°C led to a pH- and time-dependent release of the receptor into the medium. The pH optimum for release was 5.5 in the Golgi-endosomal fraction and 7.5 in plasma membrane fractions; at this pH, approximately 2% and 20%–30% of total receptors were released per hour, respectively. Receptor release was inhibited in a dose-dependent manner by aprotinin, benzamidine, and leupeptin in the Golgi-endosomal fraction, and by 1,10 phenanthroline in plasma membrane fractions, although high concentrations were required for inhibition. The receptor released from Golgi-endosomes showed a 5–10 kDa reduction in size and a loss of ability to recognize antibody anti-22C, but that released from plasma membranes showed little or no changes in size. We conclude that soluble, carboxy-terminally truncated forms of the IGF-II–M6P receptor are generated from the intact receptor in isolated Golgi-endosomal and plasma membrane fractions. However, receptor processing in these fractions exhibits different properties, suggesting the involvement of different proteases.Key words: insulin-like growth factor-II–mannose 6-phosphate (IGF-II–M6P) receptor, liver, plasma membrane, Golgi apparatus, endosomes.


1999 ◽  
Vol 84 (2) ◽  
pp. 611-617 ◽  
Author(s):  
Michael Costello ◽  
Robert C. Baxter ◽  
Carolyn D. Scott

The soluble form of the insulin-like growth factor II/mannose 6-phosphate (IGF-II/M6-P) receptor has been detected in serum from a variety of mammalian species. We report the development of a highly sensitive quantitative human IGF-II/M6-P receptor immunoassay. Antibodies raised to receptor purified from a human hepatoma cell line by phosphomannan affinity chromatography were used to develop a specific enzyme-linked immunosorbent assay. In this assay, the serum level of soluble receptor for healthy adult subjects was 0.70 ± 0.23 mg/L. We have shown that soluble receptor is developmentally regulated, with levels in infant (1.12 ± 0.28 mg/L) and prepubertal (1.18 ± 0.6 mg/L) subjects dropping by 40% during adolescence (0.73 ± 0.61 mg/L) and remaining constant throughout adulthood. Further, the receptor is gestationally regulated, with a highly significant association between gestational age and maternal serum receptor levels (r = 0.947; P < 0.0001). Noninsulin-dependent diabetes mellitus (0.98 ± 0.25 mg/L) and insulin-dependent diabetes mellitus (0.98 ± 0.25 mg/L) mildly elevated soluble receptor levels, whereas end-stage renal failure (0.75 ± 0.23 mg/L) and acromegaly (0.79 ± 0.25 mg/L) did not affect receptor levels. Additionally, we have shown that soluble receptor is present in amniotic fluid, but at a 100-fold lower concentration than serum levels. The ability to quantitate soluble IGF-II/M6-P receptor levels in serum and other fluids provides a valuable tool that will help to further elucidate the role of the receptor in human physiology and disease states.


1986 ◽  
Vol 261 (28) ◽  
pp. 13144-13150 ◽  
Author(s):  
A L Brown ◽  
D E Graham ◽  
S P Nissley ◽  
D J Hill ◽  
A J Strain ◽  
...  

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