Binding of a diphosphotyrosine-containing peptide that mimics activated platelet-derived growth factor receptor beta induces oligomerization of phosphatidylinositol 3-kinase.

The Journal of Biological Chemistry
M J LaytonM D Waterfield

Abstract

Phosphatidylinositol 3-kinase (PI3K) is a heterodimeric enzyme comprising a p110 catalytic subunit and a p85 regulatory subunit. We have recently shown that the isolated p85 subunit exists as a dimer; therefore, we examined whether the heterodimeric enzyme was capable of further self-association. Size-exclusion chromatography demonstrated that PI3K was a 1:1 complex of p85 and p110 under native conditions. However, binding of a diphosphotyrosine-containing peptide that mimics an activated platelet-derived growth factor receptor beta induced an increase in the apparent molecular mass of PI3K. This increase was due to dimerization of PI3K and was dependent on PI3K concentration but not diphosphopeptide concentration. Dimer formation was also observed directly using fluorescence resonance energy transfer. Diphosphopeptide-induced activation of PI3K (Carpenter, C. L., Auger, K. R., Chanudhuri, M., Yoakim, M., Schaffhausen, B., Shoelson, S., and Cantley, L. C. (1993) J. Biol. Chem. 268, 9478-9483; Rordorf-Nikolic, T., Van Horn, D. J., Chen, D., White, M. F., and Backer, J. M. (1995) J. Biol. Chem. 270, 3662-3666) was not a direct result of dimerization and occurred only when phosphatidylinositol, and not phosphatidylinositol-4,5-dip...Continue Reading

References

Sep 1, 1992·Neuron·J Schlessinger, A Ullrich
Feb 1, 1992·Molecular and Cellular Biology·N RedemannA Ullrich
Jan 1, 1983·Methods in Enzymology·F E Regnier
Jun 21, 1994·Proceedings of the National Academy of Sciences of the United States of America·M Eigen, R Rigler
Jul 28, 1995·The Journal of Biological Chemistry·K F ToliasC L Carpenter
Mar 12, 1993·Cell·Z SongyangR J Lechleider
Jan 5, 1995·Biochemical and Biophysical Research Communications·G G FreundR A Mooney
Aug 18, 1994·Nature·P Rodriguez-VicianaJ Downward
Feb 1, 1994·Current Opinion in Genetics & Development·R J Mourey, J E Dixon
Jan 1, 1993·The Biochemical Journal·F ShibasakiT Takenawa
Feb 29, 1996·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·M J ZvelebilF Pages
Dec 10, 1996·Proceedings of the National Academy of Sciences of the United States of America·A MusacchioS C Harrison
Apr 29, 1997·Proceedings of the National Academy of Sciences of the United States of America·B VanhaesebroeckM D Waterfield
Jul 1, 1997·Trends in Biochemical Sciences·B VanhaesebroeckM D Waterfield

❮ Previous
Next ❯

Citations

Jan 22, 2008·The Journal of Biological Chemistry·Dipak BaruaJason M Haugh
Jan 20, 2004·Molecular and Cellular Biology·Lazaros C FoukasPeter R Shepherd
Aug 16, 2001·Proceedings of the National Academy of Sciences of the United States of America·H H NandurkarC A Mitchell
Jan 26, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Pradipta Ghosh
Aug 19, 2009·The Psychoanalytic Quarterly·Ken Corbett
Jun 2, 2011·The Psychoanalytic Quarterly·Ken Corbett
Jul 30, 2015·ELife·Lydia W T CheungGordon B Mills
Jun 25, 2014·Molecular and Cellular Biology·Vicente Pérez-GarcíaAna C Carrera
Aug 28, 2002·The Journal of Biological Chemistry·Concepcion JimenezAna C Carrera
Oct 9, 2007·Cell Biology International·Jing-Feng GuoXiao-Feng Zhu
Dec 13, 2005·The Journal of Biological Chemistry·Lijun LiuG Wayne Zhou
Jun 5, 2004·Biochemical and Biophysical Research Communications·Lazaros C Foukas, Peter R Shepherd

❮ 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.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.