Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/116011
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Type: Journal article
Title: Insulin- like growth factor- II ( IGF- II) and IGF- II analogs with enhanced insulin receptor- a binding affinity promote neural stem cell expansion
Author: Ziegler, A.N.
Chidambaram, S.
Forbes, B.E.
Wood, T.L.
Levison, S.W.
Citation: Journal of Biological Chemistry, 2014; 289(8):4626-4633
Publisher: American Society for Biochemistry and Molecular Biology
Issue Date: 2014
ISSN: 0021-9258
1083-351X
Statement of
Responsibility: 
Amber N Ziegler, Shravanthi Chidambaram, Briony E. Forbes, Teresa L. Wood and Steven W. Levison
Abstract: The objective of this study was to employ genetically engineered IGF-II analogs to establish which receptor(s) mediate the stemness promoting actions of IGF-II on mouse subventricular zone neural precursors. Neural precursors from the subventricular zone were propagated in vitro in culture medium supplemented with IGF-II analogs. Cell growth and identity were analyzed using sphere generation and further analyzed by flow cytometry. F19A, an analog of IGF-II that does not bind the IGF-2R, stimulated an increase in the proportion of neural stem cells (NSCs) while decreasing the proportion of the later stage progenitors at a lower concentration than IGF-II. V43M, which binds to the IGF-2R with high affinity but which has low binding affinity to the IGF-1R and to the A isoform of the insulin receptor (IR-A) failed to promote NSC growth. The positive effects of F19A on NSC growth were unaltered by the addition of a functional blocking antibody to the IGF-1R. Altogether, these data lead to the conclusion that IGF-II promotes stemness of NSCs via the IR-A and not through activation of either the IGF-1R or the IGF-2R.
Keywords: Stem cells; central nervous system; cell proliferation; self-renewal; insulin receptor; neurodevelopment; insulin; receptor tyrosine kinase
Rights: Copyright 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
RMID: 0030025135
DOI: 10.1074/jbc.M113.537597
Appears in Collections:Medicine publications

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