Osmotic loading of neutralizing antibodies demonstrates a role for protein-tyrosine phosphatase 1B in negative regulation of the insulin action pathway.

The Journal of Biological Chemistry
F AhmadB J Goldstein

Abstract

Protein-tyrosine phosphatases (PTPases) have been postulated to balance the steady-state phosphorylation and the activation state of the insulin receptor and its substrate proteins. To explore whether PTP1B, a widely expressed, non-receptor-type PTPase, regulates insulin signaling, we used osmotic shock to load rat KRC-7 hepatoma cells with affinity-purified neutralizing antibodies that immunoprecipitate and inactivate the enzymatic activity of recombinant rat PTP1B in vitro. In cells loaded with PTP1B antibody, insulin-stimulated DNA synthesis and phosphatidylinositol 3'-kinase activity were increased by 42% and 38%, respectively, compared with control cells loaded with preimmune IgG (p < 0.005). In order to characterize the potential site(s) of action of PTP1B in insulin signaling, we also determined that insulin-stimulated receptor autophosphorylation and insulin receptor substrate 1 tyrosine phosphorylation were increased 2.2- and 2.0-fold, respectively, and that insulin-stimulated receptor kinase activity toward an exogenous peptide substrate was increased by 57% in the PTP1B antibody-loaded cells. Osmotic loading did not alter the cellular content of PTP1B protein, suggesting that the antibody acts in the cell by sterical...Continue Reading

References

Nov 11, 1992·Proceedings of the National Academy of Sciences of the United States of America·M G MyersM F White
Apr 1, 1992·The Journal of Cell Biology·T A Woodford-ThomasJ E Dixon
Sep 30, 1992·International Journal of Cancer. Journal International Du Cancer·S FumagalliL Larizza
Aug 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·D L Brautigan, F M Pinault
Feb 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·N B RudermanL C Cantley
Feb 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·K L GuanJ E Dixon
Apr 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·J ChernoffB G Neel
Jul 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·M F CicirelliE G Krebs
Jul 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·H CharbonneauK A Walsh
Sep 15, 1983·Biochemical and Biophysical Research Communications·G GrunbergerP Gorden
Jan 31, 1995·Proceedings of the National Academy of Sciences of the United States of America·K YamauchiJ E Pessin
Feb 10, 1995·The Journal of Biological Chemistry·D T KulasR A Mooney

❮ Previous
Next ❯

Citations

Apr 13, 2000·Journal of Cellular Biochemistry·S J DyllaR W Hardy
Mar 12, 2004·Bioorganic & Medicinal Chemistry Letters·Cheuk K LauGiovana Scapin
Apr 15, 2004·Bioorganic & Medicinal Chemistry Letters·Michel ThérienChidambaram Ramachandran
Mar 23, 2005·Current Opinion in Cell Biology·Annie BourdeauMichel L Tremblay
Jul 10, 2003·Life Sciences·Aparecida Emiko HirataMario José Abdalla Saad
Aug 23, 2002·Pharmacology & Therapeutics·Zhong-Yin ZhangLaiping Xie
Apr 21, 1999·Biochimica Et Biophysica Acta·Q WangC Ramachandran
Feb 27, 2001·Molecular and Cellular Endocrinology·X Y WangJ E Bleasdale
Aug 5, 1999·Cellular Signalling·F H Nystrom, M J Quon
Apr 1, 2000·Bioorganic & Medicinal Chemistry Letters·O A IbrahimiZ Y Zhang
May 18, 2001·Trends in Cell Biology·A Ostman, F D Böhmer
Feb 12, 2002·Bioorganic & Medicinal Chemistry·V Sreenivasa Murthy, Vithal M Kulkarni
Jul 20, 2004·Nature Structural & Molecular Biology·Christian WiesmannStig K Hansen
Feb 22, 2002·European Journal of Biochemistry·Alan ChengMichel L Tremblay
Feb 12, 2009·The Journal of Biological Chemistry·Valeria E P ZarelliClaudia N Tomes
Sep 1, 2007·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Mariana A CalleroAlcira B Nesse
Jul 30, 2009·Journal of Lipid Research·Raju V S Rajala
Nov 5, 2008·Biological & Pharmaceutical Bulletin·Myung Sun Lee, Cheon Bae Sohn
Feb 25, 2009·Bioinformation·Neelam VermaRaman Kumar Verma

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antibody Specificity

Antibodies produced by B cells are highly specific for antigen as a result of random gene recombination and somatic hypermutation and affinity maturation. As the main effector of the humoral immune system, antibodies can neutralize foreign cells. Find the latest research on antibody specificity here.

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.