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Titolo:
Toward understanding the role of insulin alpha-helix II in the growth-promoting activity of insulin
Autore:
Chen, H; Feng, YM;
Indirizzi:
Chinese Acad Sci, State Key Lab Mol Biol, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China Chinese Acad Sci Shanghai Peoples R China 200031 200031, Peoples R China
Titolo Testata:
BIOLOGICAL CHEMISTRY
fascicolo: 7, volume: 382, anno: 2001,
pagine: 1057 - 1062
SICI:
1431-6730(200107)382:7<1057:TUTROI>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECEPTOR-BINDING; HYBRID; AMPHIOXUS; CHAIN; EVOLUTION; PEPTIDE; 1.5-A; IGF-1;
Keywords:
growth-promoting activity; insulin; insulin-like growth factor 1 (IGF-1); molecular scaffold; structural motif;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
31
Recensione:
Indirizzi per estratti:
Indirizzo: Feng, YM Chinese Acad Sci, State Key Lab Mol Biol, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, 320 Yue Tang Rd, Shanghai 200031, Peoples R China Chinese Acad Sci 320 Yue Tang Rd Shanghai Peoples R China 200031
Citazione:
H. Chen e Y.M. Feng, "Toward understanding the role of insulin alpha-helix II in the growth-promoting activity of insulin", BIOL CHEM, 382(7), 2001, pp. 1057-1062

Abstract

For further understanding the contribution of the alpha -helix II (alpha II) in the growth-promoting activity of insulin, the residues A2IIe, A5Gln, and A8Thr located in alpha II were mutated to Leu, Glu, and Tyr, respectively. Three mutant insulins, [A2Leu]human insulin, [A5Glu]human insulin, and [A8Tyr]human insulin, were prepared by means of site-directed mutagenesis. The in vitro growth-promoting activities of the three mutant insulins, measured using GR2H6 cells, were 7.5%, 291%, and 250% of that of native insulin, respectively. Their receptor-binding activities to the insulin receptor were 2.3%, 46.7%, and 138.7%, respectively, compared with native insulin. Both the growth-promoting and receptor-binding activities of [A2Leu]human insulin and [A3Leu]insulin (Shi et al., 1997) were parallel and greatly decreased compared with native insulin. The results demonstrate that the residuesA2IIe and A3Val in the all are essential for the growth-promoting activityof insulin, and the growth-promoting function of insulin might be performed through, or mainly through, binding to the insulin receptor. The growth-promoting activities of [A5Glu]human insulin and [A8Tyr]human insulin were increased 6-fold and 2-fold, respectively, compared with native insulin, indicating that their growth-promoting activities might be expressed by, or mainly by, binding to the IGF-1 receptor.

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Documento generato il 27/01/20 alle ore 07:53:56