Document Detail

Insulin-like growth factor-II is a substrate for dipeptidylpeptidase I (cathepsin C). Biological properties of the product.
MedLine Citation:
PMID:  7957246     Owner:  NLM     Status:  MEDLINE    
We observed that the lysosomal enzyme, dipeptidylaminopeptidase I (DAP-I) caused the release of trichloroacetic-acid-soluble radioactivity from rat 125I-insulin-like growth factor-II (IGF-II). This activity could be blocked by dipeptide inhibitors of DAP-I, and was enhanced by chloride. Treatment of unlabeled rat IGF-II with DAP-I converted approximately 50% of the IGF-II to a species with a slightly shorter elution time on reverse-phase HPLC, whereas treatment of human IGF-II caused complete conversion to the species with the shorter elution time. Rat IGF-II purified from the rat BRL 3A cell line is a mixture of two molecules beginning with Ala-Tyr-Arg-Pro-Ser- and Tyr-Arg-Pro-Ser- [Marquardt, H., Todaro, G. J., Henderson, L. E. & Oroszlan, S. (1981) J. Biol. Chem. 256, 6859-6865] while human IGF-II begins with Ala-Tyr-Arg-Pro-Ser-. Determination of the N-terminal amino acid sequence of human IGF-II before and after digestion with DAP-I showed that DAP-I cleaved Ala-Tyr, terminating at Arg-Pro-; the rat IGF-II species beginning with Tyr-Arg-Pro-Ser- was resistant to digestion. In order to compare DAP-I-treated IGF-II with native IGF-II for binding to IGF receptors and IGF-binding proteins and in a bioassay, rat and human IGF-II were treated with DAP-I and the digested and undigested species were isolated by reverse-phase HPLC. The IGF-II/mannose 6-phosphate receptor was purified from rat placental membranes, the IGF-I receptor was solubilized from human placental membranes and IGF-binding proteins were partially purified from adult and three-day-old rat sera by sequential gel filtration on Sephadex G-200 (pH 8.0) and Sephadex G-50 (acid pH). The dose/response curves of the two IGF-II species were indistinguishable in radioreceptor assays utilizing the IGF-II/mannose 6-phosphate receptor and the IGF-I receptor and in IGF competitive binding assays utilizing partially purified IGF-binding proteins. The DAP-I-digested and native IGF-II species were also equipotent in stimulating [3H]thymidine incorporation into DNA in the human osteosarcoma cell line, MG-63. We conclude that DAP-I cleaves an N-terminal dipeptide from IGF-II and that this does not result in a change in the biological activity of the molecule.
W Kiess; C Terry; W H Burgess; B Linder; W Lopaczynski; P Nissley
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  European journal of biochemistry / FEBS     Volume:  226     ISSN:  0014-2956     ISO Abbreviation:  Eur. J. Biochem.     Publication Date:  1994 Nov 
Date Detail:
Created Date:  1994-12-28     Completed Date:  1994-12-28     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0107600     Medline TA:  Eur J Biochem     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  179-84     Citation Subset:  IM    
Metabolism Branch, National Cancer Institute, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda.
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MeSH Terms
Amino Acid Sequence
Cathepsin C
Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / metabolism*
Insulin-Like Growth Factor II / metabolism*
Molecular Sequence Data
Substrate Specificity
Reg. No./Substance:
67763-97-7/Insulin-Like Growth Factor II; EC 3.4.14.-/Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; EC C

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