The p85alpha subunit of phosphatidylinositol 3'-kinase binds to and stimulates the GTPase activity of Rab proteins

The Journal of Biological Chemistry
M Dean ChamberlainDeborah H Anderson

Abstract

Rab5 and Rab4 are small monomeric GTPases localized on early endosomes and function in vesicle fusion events. These Rab proteins regulate the endocytosis and recycling or degradation of activated receptor tyrosine kinases such as the platelet-derived growth factor receptor (PDGFR). The p85alpha subunit of phosphatidylinositol 3'-kinase contains a BH domain with sequence homology to GTPase activating proteins (GAPs), but has not previously been shown to possess GAP activity. In this report, we demonstrate that p85alpha has GAP activity toward Rab5, Rab4, Cdc42, Rac1 and to a lesser extent Rab6, with little GAP activity toward Rab11. Purified recombinant Rab5 and p85alpha can bind directly to each other and not surprisingly, the p85alpha-encoded GAP activity is present in the BH domain. Because p85alpha stays bound to the PDGFR during receptor endocytosis, p85alpha will also be localized to the same early endosomal compartment as Rab5 and Rab4. Taken together, the physical co-localization and the ability of p85alpha to preferentially stimulate the down-regulation of Rab5 and Rab4 GTPases suggests that p85alpha regulates how long Rab5 and Rab4 remain in their GTP-bound active state. Cells expressing BH domain mutants of p85 show a...Continue Reading

References

Sep 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·J NilssonA Wasteson
Jan 1, 1995·Methods in Enzymology·A J Self, A Hall
Oct 24, 1995·Proceedings of the National Academy of Sciences of the United States of America·G LiP D Stahl
Dec 1, 1994·The Journal of Cell Biology·O MartinezB Goud
Jun 1, 1993·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·A Sorkin, C M Waters
May 1, 1996·The Biochemical Journal·G M BokochA E Traynor-Kaplan
Sep 27, 1996·The Journal of Biological Chemistry·H StenmarkA D'Arrigo
Dec 10, 1996·Proceedings of the National Academy of Sciences of the United States of America·A MusacchioS C Harrison
Jul 8, 1997·Proceedings of the National Academy of Sciences of the United States of America·V PatkiS Corvera
May 30, 1998·The Journal of Biological Chemistry·K Liu, G Li
Aug 11, 1998·Trends in Biochemical Sciences·K ScheffzekA Wittinghofer
Mar 2, 1999·Nature·S ChristoforidisM Zerial
Aug 17, 1999·Current Opinion in Cell Biology·P Chavrier, B Goud
Nov 13, 1999·Nature Cell Biology·S ChristoforidisM Zerial
Mar 15, 2000·The International Journal of Biochemistry & Cell Biology·J Armstrong
Sep 7, 2000·The Journal of Cell Biology·B QualmannR B Kelly
Jun 2, 2001·Genome Biology·H Stenmark, V M Olkkonen
Jan 29, 2002·Biochemical and Biophysical Research Communications·Yun FangDeborah H Anderson
Jun 1, 2002·Science·Lewis C Cantley
Jul 21, 2004·Current Opinion in Cell Biology·Miguel C Seabra, Christina Wasmeier

❮ Previous
Next ❯

Citations

Apr 9, 2005·Trends in Biochemical Sciences·Bart VanhaesebroeckLazaros C Foukas
Jun 23, 2012·Nature Reviews. Molecular Cell Biology·Steve Jean, Amy A Kiger
Mar 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Ryaz B ChagparDeborah H Anderson
Aug 10, 2011·Proceedings of the National Academy of Sciences of the United States of America·Jennifer Y LeeLewis C Cantley
Apr 5, 2008·The Journal of Biological Chemistry·M Dean ChamberlainDeborah H Anderson
Nov 1, 2008·The Journal of Biological Chemistry·Vicente A TorresDwayne Stupack
Jul 21, 2010·Current Opinion in Rheumatology·Andras PerlPaul E Phillips
Aug 30, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Kristy L HouckMark Kester
Dec 25, 2013·PloS One·Rebecca L RossMargaret A Knowles
Feb 28, 2008·International Immunology·Tomomitsu DoiShigeo Koyasu
Dec 25, 2015·Nature Reviews. Rheumatology·Andras Perl
Oct 1, 2014·Communicative & Integrative Biology·Jorge DíazVicente A Torres
Jul 30, 2015·ELife·Lydia W T CheungGordon B Mills
Aug 2, 2013·Memórias do Instituto Oswaldo Cruz·Ana Paula Carneiro SalgadoCláudio Antônio Bonjardim
Aug 2, 2005·Biochemical and Biophysical Research Communications·Xiang-Ming ZhangTony Rowe
Nov 25, 2017·Scientific Reports·Dielle E Whitecross, Deborah H Anderson
Jan 1, 2005·Arteriosclerosis, Thrombosis, and Vascular Biology·E J Landon, T Inagami
Jan 3, 2019·Endocrinology·Anne R Bresnick, Jonathan M Backer
Jan 20, 2019·The Journal of Biological Chemistry·Samantha D HeitzJonathan M Backer
Sep 27, 2012·Cytoskeleton·Arnaud Echard
Jan 18, 2019·Oncotarget·Jeremy D S MarshallDeborah H Anderson
Jul 18, 2020·Biochemical Society Transactions·Millie FoxDarerca Owen
Aug 30, 2013·Communicative & Integrative Biology·Cyril Basquin, Nathalie Sauvonnet
Sep 8, 2011·Cancer Science·Po-Sheng YangChin-Wen Chi

❮ Previous
Next ❯

Related Concepts

Related Feeds

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.

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.