Regulation of proto-Dbl by intracellular membrane targeting and protein stability.

The Journal of Biological Chemistry
Cristina VanniAlessandra Eva

Abstract

The pleckstrin homology (PH) domain of onco-Dbl, a guanine nucleotide exchange factor (GEF) for Cdc42 and RhoA GTPases, interacts with phosphoinositides (PIPs). This interaction modulates both the GEF activity and the targeting to the plasma membrane of onco-Dbl. Conversely, we have previously shown that in proto-Dbl an intramolecular interaction between the N-terminal domain and the PH domain imposes a negative regulation on both the DH and PH functions, suppressing its transforming activity. Here we have further investigated the mode of regulation of proto-Dbl by generating proto-Dbl mutants deleted of the last C-terminal 50 amino acids, which contain a PEST motif, and/or unable to bind to PIPs due to substitutions of the positively charged residues of the PH domain. The PH mutants of proto-Dbl retained a relative weak GEF activity toward Cdc42 and RhoA in vitro, but their RhoA activating potential was impaired in vivo. Further, these mutants lost both the plasma membrane targeting and the transforming activities, contrary to the PH mutants of onco-Dbl that retained the exchange activity both in vitro and in vivo and showed significant, but partially, reduced transforming activity. Deletion of the C-terminal sequences from on...Continue Reading

References

Apr 1, 1973·Virology·F L Graham, A J van der Eb
Apr 1, 1996·Current Opinion in Cell Biology·R A Cerione, Y Zheng
Feb 15, 1997·Genes & Development·R PeronaJ C Lacal
Oct 6, 1997·Genes & Development·L Van Aelst, C D'Souza-Schorey
Feb 7, 1998·Science·A Hall
Feb 20, 1999·The Journal of Biological Chemistry·S FukuharaJ S Gutkind
Mar 24, 1999·The Journal of Cell Biology·A Nern, R A Arkowitz
Apr 23, 1999·The Journal of Biological Chemistry·I N FlemingJ H Exton
Jun 22, 1999·FEBS Letters·M Katan, V L Allen
Oct 19, 1999·Molecular and Cellular Biology·I P WhiteheadC J Der
Jun 6, 2000·The Journal of Biological Chemistry·K KimuraS Narumiya
Nov 4, 2000·Biochemical and Biophysical Research Communications·S Jin, J H Exton
Jan 3, 2001·Molecular and Cellular Biology·K ZhuY Zheng
Mar 10, 2001·Molecular and Cellular Biology·F BiY Zheng
Dec 12, 2001·Trends in Biochemical Sciences·Y Zheng

❮ Previous
Next ❯

Citations

Jun 11, 2008·Proceedings of the National Academy of Sciences of the United States of America·T K SmithD M Bader
Jun 30, 2011·The Journal of Biological Chemistry·Marzia OgnibeneAlessandra Eva
Dec 21, 2006·Molecular and Cellular Biology·Elena KamyninaDanny Manor
Apr 27, 2004·Molecular Cancer·Christina CurtisNora Heisterkamp
May 24, 2011·Clinical Lipidology·Aaron H NileAby Grabon
Jun 28, 2003·FEBS Letters·Alexander E MertensJohn G Collard
May 13, 2008·International Journal of Cancer. Journal International Du Cancer·Masanao MurakamiErle S Robertson
Aug 27, 2003·The Journal of Biological Chemistry·Lei WangYi Zheng
Mar 15, 2003·The Journal of Biological Chemistry·Kent L RossmanJohn Sondek
Aug 19, 2007·The Journal of Biological Chemistry·Mark A BarberHeidi C E Welch
Mar 6, 2007·The Journal of Biological Chemistry·Marielle E YoheJohn Sondek
Jan 1, 2015·Journal of Molecular Signaling·Mingda YanDanny N Dhanasekaran
Dec 22, 2004·The Journal of Biological Chemistry·Huajun QinJeffrey A Frost

❮ 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.