A Pak- and Pix-dependent branch of the SDF-1alpha signalling pathway mediates T cell chemotaxis across restrictive barriers

The Biochemical Journal
Natalia VolinskyD Yablonski

Abstract

Pak (p21-activated kinase) serine/threonine kinases have been shown to mediate directional sensing of chemokine gradients. We hypothesized that Pak may also mediate chemokine-induced shape changes, to facilitate leucocyte chemotaxis through restrictive barriers, such as the extracellular matrix. A potent inhibitor, Pak(i), was characterized and used to probe the role of Pak-family kinases in SDF-1alpha (stromal-cell derived factor-1alpha/CXCL12)-induced chemotaxis in a T cell model. Pak(i) potently inhibited SDF-1alpha-induced Pak activation by a bivalent mechanism, as indicated by its complete inactivation upon point mutation of two binding sites, but partial inactivation upon mutation of either site alone. Importantly, Pak(i) was not toxic to cells over the time frame of our experiments, since it did not substantially affect cell surface expression of CXCR4 (CXC chemokine receptor 4) or integrins, cell cycle progression, or a number of ligand-induced responses. Pak(i) produced dose-dependent inhibition of SDF-1alpha-induced migration through rigid filters bearing small pores; but unexpectedly, did not substantially affect the magnitude or kinetics of chemotaxis through filters bearing larger pores. SDF-1alpha-induced Pak acti...Continue Reading

References

Nov 1, 1984·The Journal of Experimental Medicine·A Weiss, J D Stobo
May 1, 1996·Current Biology : CB·J L BrownJ Chant
Mar 1, 1997·Current Biology : CB·M A SellsJ Chernoff
Sep 3, 1998·The Journal of Biological Chemistry·S BagrodiaR A Cerione
Dec 22, 1998·Molecular and Cellular Biology·H Tu, M Wigler
Feb 2, 1999·The EMBO Journal·F Sánchez-Madrid, M A del Pozo
May 20, 1999·The Journal of Cell Biology·M A SellsJ Chernoff
Mar 29, 2001·Nature Immunology·B Moser, P Loetscher
Mar 29, 2001·Nature Immunology·M Thelen
Jul 18, 2001·The Journal of Clinical Investigation·I S ZeelenbergE Roos
Oct 10, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·H GeminderA Ben-Baruch
Mar 14, 2002·Current Opinion in Cell Biology·Orion D Weiner
May 30, 2002·Biochemistry·Dingzhi WangAnn Richmond
Jun 25, 2002·Nature Cell Biology·Orion D WeinerHenry R Bourne
Jan 29, 2003·The Journal of Cell Biology·Supriya SrinivasanHenry R Bourne
Apr 5, 2003·Annual Review of Biochemistry·Gary M Bokoch
May 2, 2003·Nature Reviews. Cancer·Peter Friedl, Katarina Wolf
Jul 30, 2003·Cancer Metastasis Reviews·Ratna K Vadlamudi, Rakesh Kumar
Sep 13, 2003·Immunological Reviews·Daniel J CampbellEugene C Butcher
Dec 6, 2003·Science·Anne J RidleyAlan Rick Horwitz
Mar 24, 2004·Current Opinion in Cell Biology·Carole A Parent
Mar 24, 2004·Current Opinion in Cell Biology·Peter Friedl
Aug 5, 2004·The Journal of Biological Chemistry·Cornelia Weiss-HaljitiChristian Rommel
Aug 28, 2004·Journal of Cell Science·Clemens HofmannJonathan Chernoff
Aug 31, 2004·The Journal of Biological Chemistry·Rebecca A StocktonMartin Alexander Schwartz

❮ Previous
Next ❯

Citations

Aug 10, 2007·Breast Cancer Research and Treatment·Ming ZhaoIngrid U Schraufstatter
Oct 21, 2006·Nature Immunology·Matthew F Krummel, Ian Macara
Oct 25, 2012·Proceedings of the National Academy of Sciences of the United States of America·Bettina StolpOliver T Fackler
Nov 18, 2011·Stem Cells and Development·Seong-Ho KohSeung Hyun Kim
Feb 29, 2008·Annual Review of Immunology·Janis K BurkhardtMeredith H Shaffer
Mar 27, 2009·Experimental & Molecular Medicine·Eun Young ShinEung Gook Kim
Jan 10, 2014·The Journal of Clinical Investigation·Jonathan PitcherOlimpia Meucci
May 23, 2014·Cellular and Molecular Life Sciences : CMLS·Yulia ArtemenkoPeter N Devreotes
Oct 15, 2010·Journal of Cellular Physiology·Navin K VermaYuri Volkov
Aug 22, 2009·Nature Reviews. Immunology·Victor L J Tybulewicz, Robert B Henderson
May 18, 2010·Cellular and Molecular Bioengineering·Erik S Welf, Jason M Haugh
Sep 25, 2014·European Journal of Immunology·Navin K Verma, Dermot Kelleher
Mar 16, 2007·The Biochemical Journal·Monika Weisz HubsmanAmi Aronheim
Jun 19, 2008·Cellular Signalling·Soniya Sinha, Wannian Yang

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.