Kindlin-3 mediates integrin αLβ2 outside-in signaling, and it interacts with scaffold protein receptor for activated-C kinase 1 (RACK1).

The Journal of Biological Chemistry
Chen FengSuet-Mien Tan

Abstract

Integrins are heterodimeric type I membrane cell adhesion molecules that are involved in many biological processes. Integrins are bidirectional signal transducers because their cytoplasmic tails are docking sites for cytoskeletal and signaling molecules. Kindlins are cytoplasmic molecules that mediate inside-out signaling and activation of the integrins. The three kindlin paralogs in humans are kindlin-1, -2, and -3. Each of these contains a 4.1-ezrin-radixin-moesin (FERM) domain and a pleckstrin homology domain. Kindlin-3 is expressed in platelets, hematopoietic cells, and endothelial cells. Here we show that kindlin-3 is involved in integrin αLβ2 outside-in signaling. It also promotes micro-clustering of integrin αLβ2. We provide evidence that kindlin-3 interacts with the receptor for activated-C kinase 1 (RACK1), a scaffold protein that folds into a seven-blade propeller. This interaction involves the pleckstrin homology domain of kindlin-3 and blades 5-7 of RACK1. Using the SKW3 human T lymphoma cells, we show that integrin αLβ2 engagement by its ligand ICAM-1 promotes the association of kindlin-3 with RACK1. We also show that kindlin-3 co-localizes with RACK1 in polarized SKW3 cells and human T lymphoblasts. Our findings s...Continue Reading

References

Mar 1, 1983·European Journal of Immunology·J E HildrethA J McMichael
Dec 9, 1993·Nature·I Giaever, C R Keese
Nov 20, 1997·The Journal of Biological Chemistry·M CsukaiD Mochly-Rosen
Jan 27, 1998·The Journal of Biological Chemistry·J Liliental, D D Chang
Sep 25, 1999·The Journal of Biological Chemistry·D A CalderwoodM H Ginsberg
Nov 11, 1999·Journal of Molecular Recognition : JMR·D G Myszka
May 10, 2000·The Journal of Biological Chemistry·D A CalderwoodM H Ginsberg
Nov 19, 2002·Molecular Pharmacology·Angela McCahillStephen J Yarwood
Feb 18, 2003·Molecular Biology of the Cell·Elisabeth A CoxAnna Huttenlocher
Oct 2, 2003·Current Opinion in Cell Biology·Christopher V Carman, Timothy A Springer
Oct 4, 2003·Science·Seiji TadokoroDavid A Calderwood
Dec 19, 2003·The Journal of Biological Chemistry·Bing-Hao LuoTimothy A Springer
Nov 13, 2004·The Journal of Biological Chemistry·Charito S BuensucesoSanford J Shattil
Oct 26, 2005·The Journal of Cell Biology·Caroline CluzelBernhard Wehrle-Haller
Feb 4, 2006·Molecular Cell·Tiila KiemaDavid A Calderwood
Aug 1, 2006·Experimental Cell Research·Siegfried UssarMarkus Moser
Jan 5, 2007·Annual Review of Immunology·Bing-Hao LuoTimothy A Springer
Jun 19, 2007·Experimental Cell Research·Ashley T Doan, Anna Huttenlocher
Oct 12, 2007·Current Opinion in Cell Biology·M Amin ArnaoutJian-Ping Xiong
Nov 23, 2007·The Biochemical Journal·Ardcharaporn VararattanavechSuet-Mien Tan
Jan 16, 2008·The Journal of Experimental Medicine·Nicole A MorinMinsoo Kim
Feb 19, 2008·Nature Medicine·Markus MoserReinhard Fässler
Apr 25, 2008·Journal of Cell Science·David R Critchley, Alexandre R Gingras
May 7, 2008·The Journal of Cell Biology·Yan-Qing MaEdward F Plow
May 17, 2008·Genes & Development·Eloi MontanezReinhard Fässler
Dec 10, 2008·Blood·Taco W KuijpersFrank Baas
Dec 17, 2008·The Journal of Biological Chemistry·Sujay Subbayya IthychandaJun Qin
Jan 2, 2009·Journal of Cell Science·Charles H Streuli
Feb 24, 2009·Nature Medicine·Nikolay L MalininTatiana V Byzova
Feb 24, 2009·Nature Medicine·Markus MoserReinhard Fässler
Mar 7, 2009·The Journal of General Virology·Ravikumar RajamanonmaniJulien Lescar
Mar 24, 2009·Annual Review of Immunology·Clare L Abram, Clifford A Lowell
May 16, 2009·Science·Markus MoserReinhard Fässler
Sep 19, 2009·The American Journal of Pathology·Cristina HasLeena Bruckner-Tuderman

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Citations

Oct 4, 2013·Proceedings of the National Academy of Sciences of the United States of America·Federico A MorettiReinhard Fässler
Nov 8, 2012·The Journal of Biological Chemistry·Luke A YatesRobert J C Gilbert
Dec 5, 2012·Current Opinion in Hematology·Estelle S HarrisGuy A Zimmerman
Jan 31, 2014·Frontiers of Medicine·Feng YeMark H Ginsberg
Feb 11, 2015·The Journal of Cell Biology·William A ComrieJanis K Burkhardt
Dec 21, 2012·Molecular Immunology·Sarah SchmidtMarkus Sperandio
Apr 6, 2016·The Journal of Cell Biology·Kamila BledzkaEdward F Plow
Aug 15, 2013·Seminars in Cell & Developmental Biology·Dolores D MrukC Yan Cheng
Nov 3, 2016·Cell Adhesion & Migration·Chen FengSuet-Mien Tan
Jan 13, 2015·Journal of Proteomics·Brian J HareMartyn Botfield
Sep 29, 2017·Journal of Cell Science·Juan GaoYan-Qing Ma
Dec 16, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Li-Teng OngSuet-Mien Tan
Aug 9, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Navin Kumar Verma, Dermot Kelleher
Jan 6, 2016·Journal of Cell Science·Emanuel RognoniReinhard Fässler
Aug 14, 2015·Journal of Molecular Recognition : JMR·Line M MyklebustArnt J Raae
May 15, 2012·FEBS Letters·Toby J Gibson
Jun 3, 2014·Oncogene·J-J Li, D Xie
Sep 25, 2014·European Journal of Immunology·Navin K Verma, Dermot Kelleher
Jun 13, 2020·Journal of Leukocyte Biology·Vasilios A MorikisScott I Simon
Nov 13, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Neha DixitScott I Simon
Feb 20, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Thomas D Manes, Jordan S Pober
Oct 18, 2016·Current Opinion in Hematology·Anika Stadtmann, Alexander Zarbock
Feb 7, 2020·Life Science Alliance·Katarzyna BialkowskaEdward F Plow
Jan 23, 2015·Zoological Studies·Feico Mah Schuurmans StekhovenAndrew R Bottrill
Oct 14, 2020·Journal of Cell Science·Sampo KukkurainenBernhard Wehrle-Haller
Dec 9, 2020·Proceedings of the National Academy of Sciences of the United States of America·Pingfeng ZhangJinhua Wu
Jan 1, 2021·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Marcello CeciNicla Romano
Apr 30, 2021·Journal of Cell Science·Wenting BuYong-Gui Gao
Dec 18, 2013·The Journal of Allergy and Clinical Immunology·Edith van de VijverTaco W Kuijpers
Jul 17, 2021·Trends in Immunology·Audrey GérardRobert Köchl

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