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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
13
|
| pubmed:dateCreated |
1993-6-4
|
| pubmed:abstractText |
A family of six specific insulin-like growth factor binding proteins (IGFBPs) modulates the biological actions of the insulin-like growth factors, IGF-I and IGF-II. In the present study, we determined the binding affinity of purified human IGFBPs 1-6 for recombinant human IGF-II mutants whose binding to IGF-I, IGF-II/mannose 6-phosphate, and insulin receptors was previously reported (Sakano, K., Enjoh, T., Numata, F., Fujiwara, H., Marumoto, Y., Higashihashi, N., Sato, Y., Perdue, J. F., and Fujita-Yamaguchi, Y. (1991) J. Biol. Chem. 266, 20626-20635). Of the regions studied, the most important determinants of IGF-II binding to the IGFBPs were A-domain residues 48-50 and B-domain residue 26. Substitution of residues 48-50 with the analogous residues from human insulin (Thr-Ser-Ile) reduced binding to IGFBP-1, -5, and -6 more than 50-fold and to IGFBP-4 by 15-50-fold; binding to IGFBP-2 and -3 was reduced 6-12-fold. The same substitution markedly reduced binding to the IGF-II/mannose 6-phosphate receptor but not to IGF-I or insulin receptors. Although substitution of residues 54 and 55 with the analogous residues from IGF-I (Arg-Arg) abolished binding to the IGF-II/mannose 6-phosphate receptor, binding to IGFBPs was not substantially affected. Substitution of Phe26 with Ser or Leu, which decreased binding to the IGF-I and insulin receptors, reduced binding to IGFBP-1 and -6 up to 80-fold, but had lesser effects on the other IGFBPs. [Leu27]IGF-II and [Leu43]IGF-II, which had a more markedly reduced affinity for the IGF-I and insulin receptors than did [Ser26]IGF-II, were bound by the IGFBPs with relatively unchanged affinity compared with IGF-II. Thus, the determinants of IGF-II binding to IGFBPs partially overlap those for the IGF-II/mannose 6-phosphate receptor and overlap those for the IGF-I receptor to a lesser extent. IGFBP-1 and IGFBP-6 are most sensitive to changes in IGF-II structure, although IGFBP-1 binds IGF-I and IGF-II with equal affinity, whereas IGFBP-6 has a marked preferential binding affinity for IGF-II. IGF-II mutants with selective impairment in recognition by specific IGFBPs or receptors will provide a useful tool for dissecting the role of the different IGF binding macromolecules in the mediation of IGF-II actions.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor Binding...,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor Binding...,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor Binding...,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor Binding...,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor Binding...,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor Binding...,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor I,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor II,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
May
|
| pubmed:issn |
0021-9258
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
5
|
| pubmed:volume |
268
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
9246-54
|
| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:7683646-Amino Acid Sequence,
pubmed-meshheading:7683646-Amniotic Fluid,
pubmed-meshheading:7683646-Animals,
pubmed-meshheading:7683646-Binding, Competitive,
pubmed-meshheading:7683646-Carrier Proteins,
pubmed-meshheading:7683646-Female,
pubmed-meshheading:7683646-Humans,
pubmed-meshheading:7683646-Insulin-Like Growth Factor Binding Protein 1,
pubmed-meshheading:7683646-Insulin-Like Growth Factor Binding Protein 2,
pubmed-meshheading:7683646-Insulin-Like Growth Factor Binding Protein 4,
pubmed-meshheading:7683646-Insulin-Like Growth Factor Binding Protein 5,
pubmed-meshheading:7683646-Insulin-Like Growth Factor Binding Protein 6,
pubmed-meshheading:7683646-Insulin-Like Growth Factor Binding Proteins,
pubmed-meshheading:7683646-Insulin-Like Growth Factor I,
pubmed-meshheading:7683646-Insulin-Like Growth Factor II,
pubmed-meshheading:7683646-Kinetics,
pubmed-meshheading:7683646-Liver,
pubmed-meshheading:7683646-Molecular Sequence Data,
pubmed-meshheading:7683646-Mutagenesis, Site-Directed,
pubmed-meshheading:7683646-Pregnancy,
pubmed-meshheading:7683646-Rats,
pubmed-meshheading:7683646-Recombinant Proteins,
pubmed-meshheading:7683646-Sequence Deletion,
pubmed-meshheading:7683646-Sequence Homology, Amino Acid
|
| pubmed:year |
1993
|
| pubmed:articleTitle |
Binding of mutants of human insulin-like growth factor II to insulin-like growth factor binding proteins 1-6.
|
| pubmed:affiliation |
Growth and Development Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
|
| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|