Glucosylation and ADP ribosylation of rho proteins: effects on nucleotide binding, GTPase activity, and effector coupling

Biochemistry
P SehrK Aktories

Abstract

We studied the effects of glucosylation of RhoA, Rac1, and Cdc42 at threonine-35 and -37 by Clostridium difficile toxin B on nucleotide binding, GTPase activity, and effector coupling and compared these results with the ADP ribosylation of RhoA at asparagine-41 catalyzed by Clostridium botulinum C3 transferase. Whereas glucosylation and ADP ribosylation had no major effects on GDP release from RhoA, Rac1, and Cdc42, the rate of GTPgammaS release from Rho proteins was increased 3-6-fold by glucosylation. ADP ribosylation decreased the rate of GTPgammaS release by about 50%. Glucosylation reduced the intrinsic activities of the GTPases by 3-7-fold and completely blocked GTPase stimulation by Rho-GAP. In contrast, ADP ribosylation slightly increased GTPase activity ( approximately 2-fold) and had no major effect on GAP stimulation of GTPase. Whereas ADP ribosylation did not affect the interaction of RhoA with the binding domain of protein kinase N, glucosylation inhibited this interaction. Glucosylation of Rac1 markedly diminished its ability to support the activation of the superoxide-generating NADPH oxidase of phagocytes. Glucosylated Rac1 did not interfere with NADPH oxidase activation by unmodified Rac1, even when present in ...Continue Reading

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Citations

Jun 15, 2012·Archivum Immunologiae Et Therapiae Experimentalis·Paulina KleniewskaAnna Gorąca
Dec 6, 2006·Naunyn-Schmiedeberg's Archives of Pharmacology·Martin VogelsgesangKlaus Aktories
Jan 5, 2011·Naunyn-Schmiedeberg's Archives of Pharmacology·Ingo JustMarkus Hoeltje
Jan 8, 2011·Naunyn-Schmiedeberg's Archives of Pharmacology·Marta LicaHarald Genth
Apr 1, 1993·Toxicology Letters·T Boulikas
Feb 21, 2003·Biochemical and Biophysical Research Communications·Harald GenthIngo Just
Oct 12, 2001·Toxicon : Official Journal of the International Society on Toxinology·C Wilde, K Aktories
Jun 27, 2000·FEMS Microbiology Letters·M LermK Aktories
Oct 24, 2000·Current Opinion in Structural Biology·C Busch, K Aktories
Sep 16, 2000·Insect Biochemistry and Molecular Biology·M DenegriA Ivana Scovassi
Jan 5, 2002·Trends in Microbiology·Christian WildeKlaus Aktories
Apr 12, 2005·Nature Reviews. Microbiology·Klaus Aktories, Joseph T Barbieri
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Feb 6, 2013·The Journal of Biological Chemistry·Lin HongAngela Wandinger-Ness
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Mar 25, 2009·Infection and Immunity·Xiangyun HeHanping Feng
Jul 27, 2002·Annual Review of Cell and Developmental Biology·Joseph T BarbieriKlaus Aktories
Sep 13, 2008·Annual Review of Microbiology·Qing Deng, Joseph T Barbieri
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Oct 28, 2006·Proceedings of the National Academy of Sciences of the United States of America·Yury BelyiKlaus Aktories
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Oct 14, 2008·FEBS Letters·Ismael Halabi-CabezonHarald Genth

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