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https://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. |
DOI: | 10.1074/jbc.M113.537597 |
Published version: | http://dx.doi.org/10.1074/jbc.m113.537597 |
Appears in Collections: | Aurora harvest 8 Medicine publications |
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