Differential requirement for LAT and SLP-76 in GPVI versus T cell receptor signaling

The Journal of Experimental Medicine
Barbi A JuddGary A Koretzky

Abstract

Mice deficient in the adaptor Src homology 2 domain-containing leukocyte phosphoprotein of 76 kD (SLP-76) exhibit a bleeding disorder and lack T cells. Linker for activation of T cells (LAT)-deficient mice exhibit a similar T cell phenotype, but show no signs of hemorrhage. Both SLP-76 and LAT are important for optimal platelet activation downstream of the collagen receptor, GPVI. In addition, SLP-76 is involved in signaling mediated by integrin alphaIIbbeta3. Because SLP-76 and LAT function coordinately in T cell signal transduction, yet their roles appear to differ in hemostasis, we investigated in detail the functional consequences of SLP-76 and LAT deficiencies in platelets. Previously we have shown that LAT(-/-) platelets exhibit defective responses to the GPVI-specific agonist, collagen-related peptide (CRP). Consistent with this, we find that surface expression of P-selectin in response to high concentrations of GPVI ligands is reduced in both LAT- and SLP-76-deficient platelets. However, platelets from LAT(-/-) mice, but not SLP-76(-/-) mice, aggregate normally in response to high concentrations of collagen and convulxin. Additionally, unlike SLP-76, LAT is not tyrosine phosphorylated after fibrinogen binding to integri...Continue Reading

References

Sep 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·W S PearD Baltimore
Mar 31, 1995·The Journal of Biological Chemistry·J K JackmanP R Findell
Aug 16, 1996·The Journal of Biological Chemistry·J Bubeck WardenburgP R Findell
Sep 1, 1996·The Journal of Experimental Medicine·L TuostoO Acuto
Jul 8, 1997·Proceedings of the National Academy of Sciences of the United States of America·A J da SilvaC E Rudd
Jan 12, 1999·The Journal of Clinical Investigation·J L ClementsG A Koretzky
Apr 16, 1999·Immunity·W ZhangL E Samelson
Nov 11, 1999·European Journal of Immunology·Y W SuJ Wienands
Jan 15, 2000·The Journal of Biological Chemistry·S C BunnellL J Berg
Feb 12, 2000·Molecular and Cellular Biology·X R Bustelo
Apr 27, 2000·Current Opinion in Immunology·P S MyungG A Koretzky
Jun 8, 2000·Immunity·S SaitohL E Samelson
Oct 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·B A JuddG A Koretzky
Nov 30, 2000·Immunology Today·M G TomlinsonA Weiss
Dec 13, 2000·The Journal of Biological Chemistry·A ObergfellS J Shattil
Aug 4, 2001·Immunity·A FischerM Cavazzana-Calvo
Sep 22, 2001·Science·E J PetersonG A Koretzky
Jan 23, 2002·The Israel Medical Association Journal : IMAJ·Alain FischerMarina Cavazzana-Calvo

❮ Previous
Next ❯

Citations

Sep 17, 2008·Immunologic Research·Rebecca G Baker, Gary A Koretzky
Nov 18, 2006·Nature Immunology·Mark L Kahn, Gary A Koretzky
Aug 3, 2004·Nature Reviews. Immunology·Václav HorejsíBurkhart Schraven
Feb 24, 2006·Nature Reviews. Immunology·Gary A KoretzkyMichael A Silverman
Apr 20, 2010·The Journal of Biological Chemistry·James L DanielArchana Sanjay
Jul 30, 2008·The Journal of Experimental Medicine·Natalie A BezmanGary A Koretzky
Feb 1, 2012·The Journal of Experimental Medicine·Helena BlockAlexander Zarbock
May 11, 2010·Cold Spring Harbor Perspectives in Biology·Martha S Jordan, Gary A Koretzky
Aug 12, 2009·Molecular and Cellular Biology·R G BakerG A Koretzky
Jul 2, 2003·Molecular and Cellular Biology·Hong Chen, Mark L Kahn
Feb 9, 2006·BMC Molecular Biology·Timothy S FincoVictoria E Hamilton
Mar 11, 2010·Seminars in Immunopathology·Hongyan WangChristopher E Rudd
Aug 17, 2005·Journal of Thrombosis and Haemostasis : JTH·S P WatsonA C Pearce
Jul 13, 2007·Immunological Reviews·Ana Kasirer-FriedeSanford J Shattil
Jul 13, 2007·Immunological Reviews·Clare L Abram, Clifford A Lowell
Jul 13, 2007·Immunological Reviews·Natalie Bezman, Gary A Koretzky
Oct 2, 2008·Journal of Thrombosis and Haemostasis : JTH·C E HughesS P Watson
Jan 4, 2012·Immunology·Yanbo Zhang, Hongyan Wang
Jul 31, 2010·Journal of Thrombosis and Haemostasis : JTH·J V MitsiosS J Shattil
Nov 16, 2004·Seminars in Immunology·Jennifer N Wu, Gary A Koretzky
Nov 15, 2003·Immunity·Sally A NewbroughGary A Koretzky
Apr 10, 2012·Thrombosis Research·Haixia NiuT Kent Gartner
Jan 30, 2003·Nature Immunology·Martha S JordanGary A Koretzky
Feb 15, 2002·The Journal of Biological Chemistry·Darren LockeMark L Kahn
Aug 31, 2004·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Pascal MauriceFrançoise Fauvel-Lafeve
Jan 15, 2004·The Journal of Biological Chemistry·Andrew L SingerGary A Koretzky
Oct 29, 2005·Arteriosclerosis, Thrombosis, and Vascular Biology·Imke C A MunnixJohan W M Heemskerk
Oct 7, 2006·Arteriosclerosis, Thrombosis, and Vascular Biology·Frederick F Samaha, Mark L Kahn
Mar 29, 2014·Circulation Research·Yacine BoulaftaliWolfgang Bergmeier
Oct 31, 2002·Nature Immunology·Cosima T Baldari
Jun 22, 2018·Pharmacological Reviews·Jennifer YeungMichael Holinstat
Oct 24, 2006·The Biochemical Journal·Andrew C PearceSteve P Watson
Jul 5, 2003·Blood·Ben T AtkinsonSteve P Watson

❮ Previous
Next ❯

Methods Mentioned

BETA
nucleotide exchange
immunoprecipitation
Scanning Electron Microscopy
scanning
confocal microscopy
flow cytometry
transgenic

Software Mentioned

GPVI

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.