Tripathi, 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. doi:10.1096/fj.08-114124 ISSN 0892-6638.

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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 Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Journal or Publication Title:	The FASEB Journal
Publisher:	Federation of American Societies for Experimental Biology
ISSN:	0892-6638
Official Date:	2009
Dates:	Date Event 2009 Published
Volume:	Vol.23
Number:	No.8
Page Range:	pp. 2616-2626
DOI:	10.1096/fj.08-114124
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access

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