Specific activation of p85-p110 phosphatidylinositol 3'-kinase stimulates DNA synthesis by ras- and p70 S6 kinase-dependent pathways.

Molecular and Cellular Biology
J McIlroyJ M Backer

Abstract

We have developed a polyclonal antibody that activates the heterodimeric p85-p110 phosphatidylinositol (PI) 3'-kinase in vitro and in microinjected cells. Affinity purification revealed that the activating antibody recognized the N-terminal SH2 (NSH2) domain of p85, and the antibody increased the catalytic activity of recombinant p85-p110 dimers threefold in vitro. To study the role of endogenous PI 3'-kinase in intact cells, the activating anti-NSH2 antibody was microinjected into GRC + LR73 cells, a CHO cell derivative selected for tight quiescence during serum withdrawal. Microinjection of anti-NSH2 antibodies increased bromodeoxyuridine (BrdU) incorporation fivefold in quiescent cells and enhanced the response to serum. These data reflect a specific activation of PI 3'-kinase, as the effect was blocked by coinjection of the appropriate antigen (glutathione S-transferase-NSH2 domains from p85 alpha), coinjection of inhibitory anti-p110 antibodies, or treatment of cells with wortmannin. We used the activating antibodies to study signals downstream from PI 3'-kinase. Although treatment of cells with 50 nM rapamycin only partially decreased anti-NSH2-stimulated BrdU incorporation, coinjection with an anti-p70 S6 kinase antibody...Continue Reading

References

Jan 25, 1991·Cell·L C CantleyS Soltoff
Sep 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·C BetsholtzB Westermark
Sep 29, 1995·The Journal of Biological Chemistry·J ZhangS E Rittenhouse
Jul 28, 1995·The Journal of Biological Chemistry·K F ToliasC L Carpenter
Sep 8, 1995·The Journal of Biological Chemistry·D M SabatiniS H Snyder
May 1, 1995·Molecular and Cellular Biology·Q P WengJ Avruch
Jun 6, 1995·Proceedings of the National Academy of Sciences of the United States of America·S NakanishiT Balla
Jun 6, 1995·Proceedings of the National Academy of Sciences of the United States of America·Q P WengJ Avruch
Aug 18, 1994·Nature·P Rodriguez-VicianaJ Downward
Aug 1, 1994·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·R Kapeller, L C Cantley
Sep 13, 1994·Proceedings of the National Academy of Sciences of the United States of America·S RocheS A Courtneidge
May 13, 1993·Nature·H A LaneG Thomas
Dec 5, 1995·Proceedings of the National Academy of Sciences of the United States of America·L CheathamJ Blenis

❮ Previous
Next ❯

Citations

Jan 19, 2016·Neuroscience and Biobehavioral Reviews·Jesse Costales, Alexander Kolevzon
Jun 25, 2005·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Kum-Ju ParkChang-Kee Hyun
Nov 13, 1999·Nature Cell Biology·B VanhaesebroeckA J Ridley
Sep 5, 2002·Journal of Cellular Biochemistry·Claudia GentiliAna Russo De Boland
Oct 7, 2004·Cell Motility and the Cytoskeleton·Shu-Chin YipJonathan M Backer
Jul 13, 2005·The Journal of Biological Chemistry·Kuntebommanahalli N ThimmaiahPeter J Houghton
Jan 19, 2000·Leukemia·J A McCubreyA Mufson
Apr 4, 2007·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Vera P Krymskaya
Jul 13, 2002·American Journal of Physiology. Lung Cellular and Molecular Physiology·Elena A GoncharovaVera P Krymskaya
May 30, 1997·The Journal of Biological Chemistry·T JascurT Mustelin
Jun 13, 1998·The Journal of Biological Chemistry·A P KennedyR T Abraham
Mar 9, 2002·Molecular and Cellular Biology·Geert J P L KopsBoudewijn M T Burgering
Sep 26, 1997·The Journal of Biological Chemistry·D G WinklerA B Vojtek
Jul 17, 1999·The American Journal of Physiology·V P KrymskayaR A Panettieri
Oct 6, 2000·American Journal of Respiratory Cell and Molecular Biology·K PageM B Hershenson
Sep 18, 1998·Biochimica Et Biophysica Acta·C H HeldinL Rönnstrand

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antibody Specificity

Antibodies produced by B cells are highly specific for antigen as a result of random gene recombination and somatic hypermutation and affinity maturation. As the main effector of the humoral immune system, antibodies can neutralize foreign cells. Find the latest research on antibody specificity 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.