Cyclin-dependent kinase inhibitors block leukocyte adhesion and migration.

The Journal of Immunology : Official Journal of the American Association of Immunologists
Li LiuLynn M Schnapp

Abstract

Leukocyte trafficking is a tightly regulated process essential for an appropriate inflammatory response. We now report a new adhesion pathway that allows unstimulated leukocytes to adhere to and migrate through exposed endothelial matrix or high-density ligand, a process we have termed ligand-induced adhesion. This ligand-induced adhesion is integrin mediated, but in contrast to phorbol ester-stimulated adhesion, it is not dependent on the small GTPase Rap-1 activity. Instead, we show a critical role for cyclin-dependent kinase (Cdk) 4 in ligand-induced adhesion by three independent lines of evidence: inhibition by pharmacological inhibitors of Cdk, inhibition by dominant-negative construct of Cdk4, and inhibition by Cdk4 small interfering RNA. The major substrate of Cdk4, Rb, is not required for ligand-induced adhesion, suggesting the involvement of a novel Cdk4 substrate. We also demonstrate that Cdk4(-/-) mice have impaired recruitment of lymphocytes to the lung following injury. The finding that Cdk inhibitors can block leukocyte adhesion and migration may expand the clinical indications for this emerging class of therapeutics.

References

Oct 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·M LenterD Vestweber
Dec 24, 1993·Science·S van den Heuvel, E Harlow
Jun 1, 1997·Genes & Development·J LukasJ Bartek
Apr 8, 1998·Current Opinion in Genetics & Development·S Mittnacht
Oct 24, 1998·The Journal of Cell Biology·D S ParkL A Greene
Dec 18, 1998·The Journal of Biological Chemistry·A J GarcíaD Boettiger
Sep 22, 1999·Molecular and Cellular Biology·T TsutsuiH Kiyokawa
Jan 7, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·J R ChanM I Cybulsky
Mar 23, 2000·The Journal of Clinical Investigation·A R de FougerollesV E Koteliansky
Oct 6, 2000·Genes & Development·J W Harbour, D C Dean
Aug 7, 2002·The American Journal of Pathology·Marcelo L Rodriguez-PueblaClaudio J Conti
Sep 13, 2002·Oncogene·Marie KnockaertLaurent Meijer
Sep 19, 2002·Trends in Pharmacological Sciences·Marie KnockaertLaurent Meijer
Dec 14, 2002·Immunity·Stefano FiorucciAntonin R de Fougerolles
Apr 26, 2003·Journal of Leukocyte Biology·A HolubA Huttenlocher
May 29, 2003·The Journal of Cell Biology·Thomas ManesLucia R Languino
Mar 23, 2004·Molecular and Cellular Neurosciences·Uk NamgungKyong-Tai Kim
Apr 22, 2004·Journal of the American Society of Nephrology : JASN·Dana GherardiPeter J Nelson
Sep 29, 2004·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Shomron Ben-Horin, Ilan Bank
Nov 17, 2004·Genes & Development·Charles J Sherr, James M Roberts
Dec 2, 2004·Nature Reviews. Cancer·Arnaud BessonJames M Roberts
Jan 5, 2005·Trends in Immunology·Douglas A SteeberThomas F Tedder
Dec 14, 2005·Proceedings of the National Academy of Sciences of the United States of America·Eiichi SatoKunle Odunsi
Apr 11, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Geoffrey I Shapiro
Nov 24, 2006·Nature·Nikolay O BukanovOxana Ibraghimov-Beskrovnaya
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Padmanee SharmaEiichi Sato
Apr 21, 2007·American Journal of Respiratory Cell and Molecular Biology·Gustavo Matute-BelloThomas R Martin

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Citations

Mar 12, 2011·British Journal of Pharmacology·Nina BerberichRobert Fürst
Dec 15, 2010·Cell Cycle·Yu-Hua ChowLynn M Schnapp
Mar 8, 2012·AIDS Research and Human Retroviruses·Yu-hua ChowLynn M Schnapp
Feb 14, 2015·Nature Communications·Joseph RobertsonMartin J Humphries
Aug 26, 2014·Clinical and Experimental Medicine·Yong XiaGuo-Quan Gao
Apr 13, 2011·PloS One·Arie J HoogendijkCatharina W Wieland

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