Deconstructing Ras signaling in the thymus.

Molecular and Cellular Biology
Robert L KortumLawrence E Samelson

Abstract

Thymocytes must transit at least two distinct developmental checkpoints, governed by signals that emanate from either the pre-T cell receptor (pre-TCR) or the TCR to the small G protein Ras before emerging as functional T lymphocytes. Recent studies have shown a role for the Ras guanine exchange factor (RasGEF) Sos1 at the pre-TCR checkpoint. At the second checkpoint, the quality of signaling through the TCR is interrogated to ensure the production of an appropriate T cell repertoire. Although RasGRP1 is the only confirmed RasGEF required at the TCR checkpoint, current models suggest that the intensity and character of Ras activation, facilitated by both Sos and RasGRP1, will govern the boundary between survival (positive selection) and death (negative selection) at this stage. Using mouse models, we have assessed the independent and combined roles for the RasGEFs Sos1, Sos2, and RasGRP1 during thymocyte development. Although Sos1 was the dominant RasGEF at the pre-TCR checkpoint, combined Sos1/RasGRP1 deletion was required to effectively block development at this stage. Conversely, while RasGRP1 deletion efficiently blocked positive selection, combined RasGRP1/Sos1 deletion was required to block negative selection. This functi...Continue Reading

References

Jan 14, 1994·Cell·K A HogquistF R Carbone
May 14, 1996·Proceedings of the National Academy of Sciences of the United States of America·W SwatF W Alt
Jul 1, 1996·The Journal of Experimental Medicine·J Alberola-IlaR M Perlmutter
Apr 16, 1999·Immunity·W ZhangL E Samelson
Aug 11, 2000·Molecular and Cellular Biology·L M EstebanE Santos
Mar 23, 2001·Nature Immunology·N A DowerJ C Stone
Sep 28, 2005·The Journal of Experimental Medicine·Jonathan S MaltzmanGary A Koretzky
Oct 4, 2005·Nature Reviews. Immunology·Kristin A HogquistStephen C Jameson
Oct 18, 2005·Immunity·April M FischerStephen M Hedrick
Aug 7, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·John J PriatelHung-Sia Teh
Dec 23, 2008·Proceedings of the National Academy of Sciences of the United States of America·Ashok PrasadArup K Chakraborty
Apr 22, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shudan ShenWeiguo Zhang
Jul 21, 2010·Nature Immunology·Andrea C Carpenter, Rémy Bosselut
Jul 13, 2011·Proceedings of the National Academy of Sciences of the United States of America·Robert L KortumLawrence E Samelson

❮ Previous
Next ❯

Citations

Mar 20, 2013·Trends in Immunology·Robert L KortumLawrence E Samelson
Nov 14, 1997·Trends in Microbiology·S H SpeckE Flemington
Mar 4, 2014·PloS One·Toshiyuki OkadaHarumi Suzuki
Apr 20, 2014·Frontiers in Biology·Olga KsiondaJeroen P Roose
Sep 18, 2013·Molecular and Cellular Biology·Fernando C BaltanásEugenio Santos
Mar 26, 2013·Molecular Immunology·Jennifer A OliverPhilip D King
Feb 6, 2014·European Journal of Immunology·Mateusz PoltorakLuca Simeoni
May 15, 2015·European Journal of Immunology·Geoffrey GuittardLawrence E Samelson
Nov 15, 2012·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Rebekah R Bartelt, Jon C D Houtman
Mar 21, 2015·PloS One·Ryunosuke MuroHarumi Suzuki
Apr 13, 2017·The Journal of Experimental Medicine·Guotong FuLinrong Lu
Jul 19, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Pengcheng ChenXiao-Ping Zhong
Dec 5, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Robert L KortumConnie L Sommers
Jun 28, 2017·The Journal of Experimental Medicine·Dominic P GolecTroy A Baldwin
Apr 4, 2017·Acta Biochimica Et Biophysica Sinica·Dongguang GuoYugu Li
Mar 6, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Wolfgang PasterOreste Acuto
Sep 12, 2015·The Journal of Biological Chemistry·Lakshmi BalagopalanLawrence E Samelson
May 1, 2021·Genes·Erin Sheffels, Robert L Kortum

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.