The Jak/Stat pathway and urokinase receptor signaling in human aortic vascular smooth muscle cells.

The Journal of Biological Chemistry
Inna DumlerD C Gulba

Abstract

The binding of urokinase plasminogen activator (uPA) to its specific receptor (uPAR) facilitates migration of vascular smooth muscle cells (VSMC). However, the signaling cascade utilized by the urokinase receptor is only incompletely understood. We investigated intracellular uPA/uPAR signaling in human aortic VSMC from the cell membrane to the nucleus. uPA binding to VSMC induced a rapid and pronounced increase in tyrosine phosphorylation of several proteins with molecular masses of 53-60, 85-90, and 130-140 kDa. By using co-immunoprecipitation techniques and in vitro kinase assays, the uPAR-associated proteins were identified as Janus (Jak) and Src non-receptor protein-tyrosine kinases (PTK) Jak1, Tyk2, and p59(fyn), p53/56(lyn), p53/59(hck), and p55(fgr). Furthermore, uPA induced a time-dependent reversible translocation of the Stat1 (signal transducer and activator of transcription) protein to the VSMC nuclei, as shown by confocal microscopy studies. Using an electrophoretic mobility shift assay, we then demonstrated that Stat1 is rapidly activated in response to stimulation with uPA and specifically binds to the DNA regulatory elements GAS (interferon-gamma activation site) and ISRE (interferon-stimulated response element)....Continue Reading

References

Sep 1, 1979·Proceedings of the National Academy of Sciences of the United States of America·H TowbinJ Gordon
Jan 1, 1985·Advances in Cancer Research·K DanøL Skriver
Nov 1, 1994·Current Biology : CB·J BriscoeM Müller
Apr 1, 1994·The Journal of Clinical Investigation·M R GyetkoR G Sitrin
Jan 29, 1993·Biochemical and Biophysical Research Communications·M Del RossoM Ruggiero
Feb 1, 1993·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·F Blasi
Aug 1, 1993·The Journal of Cell Biology·M S PepperJ D Vassalli
Apr 1, 1996·Molecular and Cellular Biology·X CaoY H Tan
Jan 1, 1996·Cellular Signalling·M B MarreroK E Bernstein
Nov 1, 1996·Trends in Biochemical Sciences·G R Crabtree, S L Schreiber
Apr 1, 1997·Proceedings of the National Academy of Sciences of the United States of America·G ConwayW Gilbert
Jun 1, 1994·Trends in Cell Biology·A ZiemieckiA F Wilks
Sep 1, 1996·Trends in Cell Biology·J BriscoeM Müller

❮ Previous
Next ❯

Citations

Mar 17, 2004·Experimental Cell Research·Manolis C DemetriouAnne E Cress
Sep 9, 2000·Current Opinion in Cell Biology·L Ossowski, J A Aguirre-Ghiso
Mar 15, 2003·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·Dina Tsatas, Andrew H Kaye
Jan 18, 2003·The International Journal of Biochemistry & Cell Biology·Zhiyu Wang, Michelle Kurpakus-Wheater
Jul 17, 1999·European Journal of Biochemistry·J A Aguirre GhisoE B de Kier Joffè
Jun 10, 2000·European Journal of Biochemistry·H L Pahl
May 18, 2007·Molecular Biology of the Cell·Audrey M BernsteinSandra K Masur
Mar 17, 2007·American Journal of Respiratory and Critical Care Medicine·Philippe BéginCatherine Laprise
Mar 1, 2000·American Journal of Respiratory Cell and Molecular Biology·D A WaltzH A Chapman
Mar 5, 2010·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Ladan Teimoori-ToolabiSirous Zeinali
Apr 17, 2009·Canadian Journal of Physiology and Pharmacology·Vsevolod A TkachukYelena V Parfyonova
Jun 18, 2011·Biochemical and Biophysical Research Communications·Natalia TkachukInna Dumler
Jul 31, 2007·Cancer Treatment Reviews·Y Li, P J Cozzi
Dec 4, 2015·Cytokine·Nicole R LeitnerMathias Müller
Feb 22, 2005·Biochemical and Biophysical Research Communications·Lirlândia P De SousaCláudio A Bonjardim
Oct 18, 2005·Biochemical and Biophysical Research Communications·Lirlândia P SousaCláudio A Bonjardim
Oct 19, 2012·Cell Adhesion & Migration·Johannes M Breuss, Pavel Uhrin
Dec 23, 1999·Current Biology : CB·I DumlerD C Gulba
Jun 6, 2007·Biochemical and Biophysical Research Communications·Margret PateckiAngelika Kusch
Feb 14, 2006·Cancer·Paulette Mhawech-FaucegliaJuerg Schwaller
Jul 3, 2003·Science's STKE : Signal Transduction Knowledge Environment·Steingrimur Stefansson, Daniel A Lawrence
Dec 4, 2002·Nature Reviews. Molecular Cell Biology·Francesco Blasi, Peter Carmeliet

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.