Molecular priming of Lyn by GPVI enables an immune receptor to adopt a hemostatic role.

Proceedings of the National Academy of Sciences of the United States of America
Alec A SchmaierMark L Kahn

Abstract

The immune receptor signaling pathway is used by nonimmune cells, but the molecular adaptations that underlie its functional diversification are not known. Circulating platelets use the immune receptor homologue glycoprotein VI (GPVI) to respond to collagen exposed at sites of vessel injury. In contrast to immune cell responses, platelet activation must take place within seconds to successfully form thrombi in flowing blood. Here, we show that the GPVI receptor utilizes a unique intracellular proline-rich domain (PRD) to accelerate platelet activation, a requirement for efficient platelet adhesion to collagen under flow. The GPVI PRD specifically binds the Src-family kinase Lyn and directly activates it, presumably through SH3 displacement. In resting platelets, Lyn is constitutively bound to GPVI in an activated state and platelets lacking Lyn exhibit defective collagen adhesion like that of platelets with GPVI receptors lacking the PRD. These findings define a molecular priming mechanism that enables an immune-type receptor to adopt a hemostatic function. These studies also demonstrate that active kinases can constitutively associate with immune-type receptors without initiating signal transduction before receptor ligation, c...Continue Reading

References

Sep 23, 2000·Nature·A J Lusis
Apr 12, 2002·The Journal of Biological Chemistry·Katsue Suzuki-InoueSteve P Watson
Feb 21, 2003·The Journal of Biological Chemistry·Darren LockeMark L Kahn
Mar 22, 2003·Blood·Bernhard Nieswandt, Steve P Watson
Jul 9, 2003·The Journal of Biological Chemistry·Teresa Bori-SanzDavid Tulasne
Aug 17, 2005·Journal of Thrombosis and Haemostasis : JTH·S P WatsonA C Pearce
Nov 2, 2005·Nature Reviews. Immunology·Gary W LitmanLarry J Dishaw
Jul 20, 2006·The Journal of Biological Chemistry·Ronald P TribleThomas E Smithgall
May 10, 2008·Nature·Wesley C WarrenRichard K Wilson
Oct 29, 2008·The Journal of Biological Chemistry·Jun MoriSteve P Watson

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Citations

Oct 16, 2012·The Journal of Biological Chemistry·Binggang XiangZhenyu Li
Jul 23, 2013·Current Opinion in Hematology·Keith B NeevesAdam R Wufsus
Aug 8, 2013·Current Opinion in Hematology·Wolfgang Bergmeier, Lucia Stefanini
Jan 26, 2012·Thrombosis and Haemostasis·M Al-TamimiR K Andrews
May 21, 2010·Biological Chemistry·Jian L QiaoRobert K Andrews
May 30, 2013·Hematology/oncology Clinics of North America·Lawrence F BrassTimothy J Stalker
Jan 31, 2015·Hämostaseologie·T VögtleB Nieswandt
Mar 30, 2010·Journal of Thrombosis and Haemostasis : JTH·S P WatsonA Y Pollitt
Jun 15, 2012·Journal of Thrombosis and Haemostasis : JTH·S SéverinS P Watson
Oct 2, 2012·Journal of Thrombosis and Haemostasis : JTH·M ZahidM Jandrot-Perrus
Mar 30, 2010·Journal of Thrombosis and Haemostasis : JTH·S EllisonY A Senis
Aug 15, 2014·Blood·Yotis A SenisJun Mori
Jun 17, 2014·Drug Discovery Today·Peng Jiang, Martine Jandrot-Perrus
May 4, 2017·Blood·Carmen H CoxonYotis A Senis
Feb 24, 2017·Physiology·Brian Estevez, Xiaoping Du
Dec 14, 2011·Arteriosclerosis, Thrombosis, and Vascular Biology·Stéphane LoyauMartine Jandrot-Perrus
Apr 4, 2015·Arteriosclerosis, Thrombosis, and Vascular Biology·Pat MetharomRobert K Andrews
Oct 8, 2014·Circulation Research·Wei LiRoy L Silverstein
Jan 12, 2019·Journal of Thrombosis and Haemostasis : JTH·Indranil BasakPaul F Bray
Jan 11, 2013·Physiological Reviews·Henri H VersteegPieter H Reitsma
Dec 2, 2017·Journal of Thrombosis and Haemostasis : JTH·L Stefanini, W Bergmeier
Feb 20, 2018·Research and Practice in Thrombosis and Haemostasis·Wolfgang Bergmeier, Lucia Stefanini
Nov 7, 2019·International Journal of Molecular Sciences·Ildikó Beke DebreceniJános Kappelmayer
Apr 26, 2021·Drug Discovery Today·Lei ZhangZhe-Sheng Chen
May 6, 2021·International Journal of Molecular Sciences·Olga ShevchukAlbert Sickmann
Jul 20, 2021·Research and Practice in Thrombosis and Haemostasis·Jessica LinKeith B Neeves
Jul 16, 2021·Research and Practice in Thrombosis and Haemostasis·Keith B Neeves

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