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IGF-independent effects of insulin-like growth factor binding protein-5 (Igfbp5) in vivo
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Tripathi, G. (Gyanendra), Salih, D. A. M., Drozd, A. C., Cosgrove, R. A., Cobb, L. J. and Pell, J. M.. (2009) IGF-independent effects of insulin-like growth factor binding protein-5 (Igfbp5) in vivo. The FASEB Journal, Vol.23 (No.8). pp. 2616-2626. ISSN 0892-6638
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Official URL: http://dx.doi.org/10.1096/fj.08-114124
Abstract
IGF activity is regulated tightly by a family of IGF binding proteins (IGFBPs). IGFBP-5 is the most conserved of these and is up-regulated significantly during differentiation of several key lineages and in some cancers. The function of IGFBP-5 in these physiological and pathological situations is unclear, however, several IGFBP-5 sequence motifs and studies in vitro suggest IGF-independent actions. Therefore, we aimed to compare the phenotypes of mice overexpressing wild-type Igfbp5 or an N-terminal mutant Igfbp5 with negligible IGF binding affinity. Both significantly inhibited growth, even at low expression levels. Even though wild-type IGFBP-5 severely disrupted the IGF axis, we found no evidence for interaction of mutant IGFBP-5 with the IGF system. Further, overexpression of wild-type IGFBP-5 rescued the lethal phenotype induced by “excess” IGF-II in type 2 receptor-null mice; mutant IGFBP-5 overexpression could not. Therefore, wild-type IGFBP-5 provides a very effective mechanism for the inhibition of IGF activity and a powerful in vivo mechanism to inhibit IGF activity in pathologies such as cancer. This study is also the first to suggest significant IGF-independent actions for IGFBP-5 during development.—Tripathi, G., Salih, D. A. M., Drozd, A. C., Cosgrove, R. A., Cobb, L. J., Pell, J. M. IGF-independent effects of insulin-like growth factor binding protein-5 (Igfbp5) in vivo.
| Item Type: | Journal Article |
|---|---|
| Divisions: | Faculty of Medicine > Warwick Medical School > Metabolic and Vascular Health Faculty of Medicine > Warwick Medical School |
| Journal or Publication Title: | The FASEB Journal |
| Publisher: | Federation of American Societies for Experimental Biology |
| ISSN: | 0892-6638 |
| Date: | 2009 |
| Volume: | Vol.23 |
| Number: | No.8 |
| Page Range: | pp. 2616-2626 |
| Identification Number: | 10.1096/fj.08-114124 |
| Status: | Peer Reviewed |
| Publication Status: | Published |
| Access rights to Published version: | Restricted or Subscription Access |
| URI: | http://wrap.warwick.ac.uk/id/eprint/44174 |
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