Autophosphorylation of cGMP-dependent protein kinase type II.

The Journal of Biological Chemistry
Arie B VaandragerHugo R de Jonge

Abstract

Cyclic nucleotides are shown to stimulate the autophosphorylation of type II cGMP-dependent protein kinase (cGK) on multiple sites. Mass spectrometric based analyses, using a quadrupole time-of-flight-mass spectrometry instrument revealed that cGMP stimulated the in vitro phosphorylation of residues Ser110 and Ser114, and, at a slow rate, of Ser126 and Thr109 or Ser117, all located in the autoinhibitory region. In addition Ser445 was found to be phosphorylated in a cGMP-dependent manner, whereas Ser110 and Ser97 were already prephosphorylated to a large extent in Sf9 cells. cGMP-dependent phosphorylation of cGK II was also demonstrated in intact COS-1 cells and intestinal epithelium. Substitution of most of the potentially autophosphorylated residues for alanines largely abolished the cGMP stimulation of the autophosphorylation. Prolonged autophosphorylation of purified recombinant cGK II in vitro resulted in a 40-50% increase in basal kinase activity, but its maximal cGMP-stimulated activity and the EC50 for cGMP remained unaltered. Mutation of the major phosphorylatable serines 110, 114, and 445 into "phosphorylation-mimicking" glutamates had no effect on the kinetic parameters of cGK II. However, replacing the slowly autopho...Continue Reading

References

Jan 2, 1986·European Journal of Biochemistry·W LandgrafF Hofmann
Sep 27, 1994·Proceedings of the National Academy of Sciences of the United States of America·T JarchauU Walter
Mar 22, 1996·The Journal of Biological Chemistry·A B VaandragerH R de Jonge
Aug 1, 1997·Trends in Biochemical Sciences·S M LohmannH R De Jonge
Mar 21, 1998·Proceedings of the National Academy of Sciences of the United States of America·A B VaandragerH R de Jonge
Oct 28, 1998·The Journal of Clinical Investigation·C WagnerA Kurtz
May 26, 1999·Proceedings of the National Academy of Sciences of the United States of America·J G HoenderopR J Bindels
Sep 16, 1999·Critical Reviews in Clinical Laboratory Sciences·S H Francis, J D Corbin
Jun 11, 2002·Biochemical and Biophysical Research Communications·Stepan GambaryanSuzanne M Lohmann
Jul 3, 2002·The Journal of Biological Chemistry·Merritt K TaylorMichael D Uhler

❮ Previous
Next ❯

Citations

Dec 7, 2010·The Journal of Biological Chemistry·Stefano ZanottiErnesto Canalis
Jun 14, 2008·The Journal of Clinical Investigation·Yosuke KawasakiHiroshi Kawaguchi
May 29, 2015·Journal of Receptor and Signal Transduction Research·Klaus StahlJohn N Forrest
Nov 17, 2004·The Journal of Biological Chemistry·Franz Hofmann
Dec 24, 2005·Physiological Reviews·F HofmannJ Schlossmann

❮ 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.