Phospholipase Cgamma/diacylglycerol-dependent activation of beta2-chimaerin restricts EGF-induced Rac signaling.

The EMBO Journal
HongBin WangMarcelo G Kazanietz

Abstract

Although receptor-mediated regulation of small G-proteins and the cytoskeleton is intensively studied, the mechanisms for attenuation of these signals are poorly understood. In this study, we have identified the Rac-GAP beta2-chimaerin as an effector of the epidermal growth factor receptor (EGFR) via coupling to phospholipase Cgamma (PLCgamma) and generation of the lipid second messenger diacylglycerol (DAG). EGF redistributes beta2-chimaerin to promote its association with the small GTPase Rac1 at the plasma membrane, as determined by FRET. This relocalization and association with Rac1 were impaired by disruption of the beta2-chimaerin C1 domain as well as by PLCgamma1 RNAi, thus defining beta2-chimaerin as a novel DAG effector. On the other hand, GAP-deficient beta2-chimaerin mutants show enhanced translocation and sustained Rac1 association in the FRET assays. Remarkably, RNAi depletion of beta2-chimaerin significantly extended the duration of Rac activation by EGF, suggesting that beta2-chimaerin serves as a mechanism that self-limits Rac activity in response to EGFR activation. Our results represent the first direct evidence of divergence in DAG signaling downstream of a tyrosine-kinase receptor via a PKC-independent mecha...Continue Reading

References

Apr 1, 1997·Current Opinion in Cell Biology·A C Newton
Apr 18, 1998·The EMBO Journal·T AzumaD J Kwiatkowski
Oct 16, 1999·Proceedings of the National Academy of Sciences of the United States of America·M J CalocaM G Kazanietz
Aug 5, 2000·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·G Carpenter
Aug 11, 2000·Molecular and Cellular Biology·S L MooresW Swat
Nov 1, 2000·Cell·D Bar-Sagi, A Hall
Jan 12, 2001·Physiological Reviews·Y TakaiT Matozaki
Nov 13, 2001·Developmental Cell·A J Ridley
Jul 9, 2002·Genes & Development·Anja Schmidt, Alan Hall
Nov 28, 2002·The Journal of Biological Chemistry·Péter TamásLászló Buday
Jan 2, 2003·The Journal of Biological Chemistry·Daria IllenbergerYoav I Henis
Mar 27, 2003·The Journal of Biological Chemistry·Jason T SnyderJohn Sondek
Jun 28, 2003·FEBS Letters·Alexander E MertensJohn G Collard
Jul 4, 2003·The EMBO Journal·María J CalocaXosé R Bustelo
Oct 25, 2003·Cellular Signalling·Raymond E Menard, Raymond R Mattingly
Nov 11, 2003·Trends in Pharmacological Sciences·ChengFeng Yang, Marcelo G Kazanietz
Dec 31, 2003·Molecular Biology of the Cell·Kazuo KurokawaMichiyuki Matsuda
May 4, 2004·Nature Reviews. Cancer·Andreas GschwindAxel Ullrich
Jun 9, 2004·Oncogene·José L ZugazaXosé R Bustelo
Jun 15, 2004·Current Opinion in Neurobiology·Nils BroseHeike Wegmeyer
May 3, 2005·The Journal of Biological Chemistry·Chengfeng YangMarcelo G Kazanietz

❮ Previous
Next ❯

Citations

Jul 31, 2007·Journal of Cancer Research and Clinical Oncology·D BreitkreutzT Tennenbaum
May 16, 2013·Nature Communications·Alvaro Gutierrez-UzquizaMarcelo G Kazanietz
Mar 27, 2007·Nature Reviews. Cancer·Erin M Griner, Marcelo G Kazanietz
Apr 2, 2011·The Journal of Biological Chemistry·HongBin WangMarcelo G Kazanietz
Feb 10, 2009·The Journal of Biological Chemistry·María Siliceo, Isabel Mérida
Oct 2, 2008·The Journal of Biological Chemistry·Francheska Colón-GonzálezMarcelo G Kazanietz
Feb 19, 2010·Molecular Biology of the Cell·Hongbin Wang, Marcelo G Kazanietz
Dec 25, 2012·Molecular Biology of the Cell·Cory M SimonLeah Edelstein-Keshet
Oct 17, 2008·American Journal of Physiology. Cell Physiology·Jaladanki N RaoJian-Ying Wang
Jan 17, 2014·Molecular Biology Reports·Lautaro Zubeldia-BrennerFederico Coluccio Leskow
Apr 18, 2007·Proceedings of the National Academy of Sciences of the United States of America·Stephen P BruinsmaThomas J Baranski
Mar 25, 2009·FEBS Letters·Shingo TakeuchiHironori Katoh
Jan 24, 2017·Molecular Carcinogenesis·Mariana CookeMarcelo G Kazanietz
Dec 14, 2006·European Journal of Immunology·Mirvat El-Sibai, Jonathan M Backer
Feb 3, 2012·Physiological Reviews·Erzsébet LigetiKlaus Scheffzek
Oct 21, 2006·Biochemical Society Transactions·H Wang, M G Kazanietz
Dec 25, 2019·The Journal of Biological Chemistry·Victoria Casado-MedranoMaría J Caloca
Feb 26, 2020·Cancers·Martin J BakerMarcelo G Kazanietz
Mar 10, 2007·The Biochemical Journal·Chengfeng Yang, Marcelo G Kazanietz
Sep 7, 2011·Cellular Signalling·Eva WertheimerMarcelo G Kazanietz
Feb 6, 2008·Cellular Signalling·María José CalocaXosé R Bustelo
Jun 26, 2012·Cell·Martin M RiccomagnoAlex L Kolodkin

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.