Targeted expression of a protease-resistant IGFBP-4 mutant in smooth muscle of transgenic mice results in IGFBP-4 stabilization and smooth muscle hypotrophy.

The Journal of Biological Chemistry
Mingyu ZhangJ A Fagin

Abstract

The insulin-like growth factor-binding protein 4 (IGFBP-4), the most abundant IGF-binding protein produced by rodent smooth muscle cells (SMC), is degraded by specific protease(s) potentially releasing IGF-I for local bioactivity. IGFBP-4 protease(s) recognizes basic residues within the midregion of the molecule. We constructed a mutant IGFBP-4 with the cleavage domain substitution 119-KHMAKVRDRSKMK-133 to 119-AAMAAVADASAMA-133. Myc-tagged native and IGFBP-4.7A retained equivalent IGF-I binding affinity. Whereas native IGFBP-4 was cleaved by SMC-conditioned medium, IGFBP-4.7A was completely resistant to proteolysis. To explore the function of the protease-resistant IGFBP-4 in vivo, expression of the mutant and native proteins was targeted to SMC of transgenic mice by means of a smooth muscle alpha-actin promoter. Transgene expression was confined to SMC-rich tissues in all lines. Bladder and aortic immunoreactive IGFBP-4/transgene mRNA ratios in SMP8-BP4.7A mice were increased by 2- to 4-fold relative to SMP8-BP4 mice, indicating that the IGFBP-4.7A protein was stabilized in vivo. SMP8-BP4.7A mice had lower aortic, bladder, and stomach weight and intestinal length relative to SMP8-BP4 counterparts matched for protein expression...Continue Reading

References

Jan 1, 1995·Progress in Growth Factor Research·J E PintarB Green
Aug 29, 1998·Molecular and Cellular Endocrinology·D R Clemmons
Aug 29, 1998·The Journal of Biological Chemistry·X QinS Mohan
Mar 17, 1999·Proceedings of the National Academy of Sciences of the United States of America·J B LawrenceC A Conover
Jan 5, 2000·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·X QinS Mohan
Feb 10, 2000·Circulation Research·A Bayes-GenisR S Schwartz
Jun 13, 2000·The Journal of Biological Chemistry·Z ShiL J Murphy
Nov 15, 2000·Molecular Endocrinology·J M ShirokawaJ A Fagin
Feb 13, 2001·Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society·D CheliusE M Spencer
Oct 6, 2001·The New England Journal of Medicine·A Bayes-GenisR S Schwartz

❮ Previous
Next ❯

Citations

Nov 11, 2008·Journal of Mammary Gland Biology and Neoplasia·D J FlintG J Allan
Sep 10, 2005·Reviews in Endocrine & Metabolic Disorders·J M PellA Drozd
May 5, 2004·Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society·Sabine MazerbourgPhilippe Monget
Sep 11, 2002·Neuromuscular Disorders : NMD·Marina BakayEric P Hoffman
Apr 26, 2003·Trends in Endocrinology and Metabolism : TEM·R Clay Bunn, John L Fowlkes
May 18, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Cheryl A ConoverMichael T Overgaard
Sep 9, 2005·International Journal of Hematology·Heike WexPeter Vorwerk
Nov 16, 2013·Cellular and Molecular Life Sciences : CMLS·H Al-KharobiJ Beattie
Feb 11, 2010·Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society·David PhangXuezhong Qin
Apr 7, 2007·Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society·David R ClemmonsWalker H Busby
Apr 10, 2007·Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society·Sylvia StrackeReinhard Friedl
Nov 3, 2015·Best Practice & Research. Clinical Endocrinology & Metabolism·Leon A Bach
Nov 16, 2004·Biochemical and Biophysical Research Communications·R Clay BunnJohn L Fowlkes
Apr 14, 2015·BioMed Research International·Varsha P BrahmkhatriHanudatta S Atreya
Apr 30, 2008·JPEN. Journal of Parenteral and Enteral Nutrition·Prue M Pereira-FantiniJulie E Bines
Dec 20, 2017·Journal of Molecular Endocrinology·L A Bach
Nov 8, 2003·Arteriosclerosis, Thrombosis, and Vascular Biology·Patrice DelafontaineYangxin Li
Dec 6, 2002·Endocrine Reviews·Sue M Firth, Robert C Baxter
Dec 19, 2008·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Mingyu LiCunming Duan
Sep 14, 2019·American Journal of Physiology. Heart and Circulatory Physiology·Lasse Bach SteffensenClaus Oxvig
Mar 7, 2021·International Journal of Molecular Sciences·Mai-Huong Thi NgoYen-Hua Huang

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.

Bladder Carcinoma In Situ

Bladder Carcinoma In Situ is a superficial bladder cancer that occurs on the surface layer of the bladder. Discover the latest research on this precancerous condition in this feed.