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DC Field | Value | Language |
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dc.contributor.author | Headey, Stephen J | en |
dc.contributor.author | Leeding, Kerri S | en |
dc.contributor.author | Norton, Raymond S | en |
dc.contributor.author | Bach, Leon A | en |
dc.date.accessioned | 2015-05-15T23:04:53Z | |
dc.date.available | 2015-05-15T23:04:53Z | |
dc.date.issued | 2004-10-01 | en |
dc.identifier.citation | Journal of Molecular Endocrinology; 33(2): 377-86 | en |
dc.identifier.govdoc | 15525596 | en |
dc.identifier.other | PUBMED | en |
dc.identifier.uri | https://ahro.austin.org.au/austinjspui/handle/1/9826 | en |
dc.description.abstract | Insulin-like growth factors IGF-I and IGF -II are important mediators of growth. A family of six high affinity IGF binding proteins (IGFBPs) modulate IGF action. IGFBPs have three domains, of which the N- and C-domains are involved in high affinity IGF binding. IGFBP-6 is unique in its 20-100-fold IGF-II binding specificity over IGF-I. The aim of this study was to determine the contributions of the N- and C-domains of IGFBP-6 to its IGF binding properties. We confirmed that differential dissociation kinetics are responsible for the IGF-II binding preference of IGFBP-6. The N-domain has rapid association kinetics, similar to full-length IGFBP-6, but both IGF-I and -II dissociate rapidly from this domain, thereby reducing its binding affinity for IGF-II approximately 50-fold. However, the N-domain binds IGF-I and -II with similar affinities and it has a similar IGF-I binding affinity to full-length IGFBP-6. This suggests that the C-domain confers the IGF-II binding preference of IGFBP-6; indeed, IGF-I bound inconsistently with very low affinity to the C-domain. Coincubation studies showed that isolated N- and C-domains of IGFBP-6 do not strongly cooperate to enhance IGF binding. The results of the binding studies are supported by the effects of the IGFBP-6 domains on IGF-induced colon cancer cell proliferation; the N-domain inhibited IGF-II induced proliferation with approximately 20-fold lower potency than IGFBP-6 and it was equipotent in inhibiting IGF-I- and IGF-II-induced proliferation. Coincubation of C-domain had no additional effect on N-domain-induced inhibition of proliferation. In conclusion, both the N- and C-domains of IGFBP-6 are involved in IGF binding, the C-domain is responsible for the IGF-II binding preference of IGFBP-6 and intact IGFBP-6 is necessary for high affinity IGF binding. | en |
dc.language.iso | en | en |
dc.subject.other | Biosensing Techniques | en |
dc.subject.other | Cell Proliferation.drug effects | en |
dc.subject.other | Colonic Neoplasms.drug therapy.metabolism.pathology | en |
dc.subject.other | Humans | en |
dc.subject.other | Insulin-Like Growth Factor Binding Protein 6.genetics.metabolism.pharmacology | en |
dc.subject.other | Insulin-Like Growth Factor I.genetics.metabolism | en |
dc.subject.other | Insulin-Like Growth Factor II.genetics.metabolism | en |
dc.subject.other | Kinetics | en |
dc.subject.other | Peptide Fragments.genetics.metabolism.pharmacology | en |
dc.subject.other | Protein Structure, Tertiary | en |
dc.subject.other | Tumor Cells, Cultured | en |
dc.title | Contributions of the N- and C-terminal domains of IGF binding protein-6 to IGF binding. | en |
dc.type | Journal Article | en |
dc.identifier.journaltitle | Journal of molecular endocrinology | en |
dc.identifier.affiliation | University of Melbourne, Department of Medicine, Austin Hospital, Heidelberg 3084, Australia | en |
dc.identifier.doi | 10.1677/jme.1.01547 | en |
dc.description.pages | 377-86 | en |
dc.relation.url | https://pubmed.ncbi.nlm.nih.gov/15525596 | en |
dc.type.austin | Journal Article | en |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.cerifentitytype | Publications | - |
item.fulltext | No Fulltext | - |
item.grantfulltext | none | - |
item.languageiso639-1 | en | - |
item.openairetype | Journal Article | - |
Appears in Collections: | Journal articles |
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