Phosphoproteomic characterization of PYK2 signaling pathways involved in osteogenesis

Journal of Proteomics
Peter C BonnetteLeonard Buckbinder

Abstract

The PYK2 tyrosine kinase is a negative regulator of bone formation, but aside from the requirement for PYK2 kinase activity there has been little progress toward understanding of the molecular mechanism involved in this function. To gain insight into the signaling pathways modulated by PYK2 we sought to identify PYK2 substrates. Challenges inherent to a quantitative phosphoproteomic analysis for non-receptor tyrosine kinases were overcome by employing an inducible PYK2 overexpression system in NIH3T3 cells in combination with a selective PYK2 inhibitor. The identification of a number of known PYK2 substrates and interacting partners validated the methodology. Results of the inducible cell system were extended to a cell model of osteogenesis, examining the effect of the PYK2 inhibitor on the phosphorylation state of targets identified in the phosphoproteomic study. Consistent with phosphoproteomic analysis, increased osteogenesis associated with a selective PYK2 inhibitor was accompanied by reduced phosphorylation of paxillin, Gab1 and p130(Cas), along with reduction of phosphorylation levels of the Met activation loop. These results further confirmed the utility of the methodology and point to a previously unknown bi-directiona...Continue Reading

References

May 1, 1995·Molecular and Cellular Biology·M D Schaller, J T Parsons
Jul 21, 1995·The Journal of Biological Chemistry·S L BellisC E Turner
Aug 6, 1996·Proceedings of the National Academy of Sciences of the United States of America·R WangJ M Bishop
Feb 13, 1999·The Journal of Biological Chemistry·P T LakkakorpiL T Duong
Jun 4, 1999·Progress in Biophysics and Molecular Biology·D D SchlaepferD J Sieg
Mar 8, 2000·Cellular Signalling·H AvrahamS Avraham
Jun 28, 2000·The Journal of Cell Biology·U SchaeperW Birchmeier
Oct 18, 2001·Molecular and Cellular Biology·P J RuestS K Hanks
Nov 7, 2001·The Biochemical Journal·M D Schaller, E M Schaefer
Jul 5, 2003·Cell Biology International·Irwin H Gelman
Sep 10, 2003·Proceedings of the National Academy of Sciences of the United States of America·M OkigakiJ Schlessinger
Apr 8, 2004·Developmental Cell·Rowena McBeathChristopher S Chen
Aug 18, 2004·Nature Biotechnology·Blagoy BlagoevMatthias Mann
Feb 16, 2005·Nature Biotechnology·Miles A FabianDavid J Lockhart
Oct 4, 2005·Cellular Signalling·Shin-Young ParkShalom Avraham
Jul 21, 2006·Proteome Science·Frédéric Delom, Eric Chevet
Aug 23, 2006·Cell·Adam J EnglerDennis E Discher
Nov 23, 2006·Nature Cell Biology·Shao-Chun WangMien-Chie Hung
Apr 5, 2007·Nature Protocols·Shao-En Ong, Matthias Mann
Jun 1, 2007·Proceedings of the National Academy of Sciences of the United States of America·Leonard BuckbinderMei Li
Aug 28, 2007·Nature Biotechnology·Marcus BantscheffGerard Drewes
Dec 13, 2007·The Journal of Biological Chemistry·Dawidson A GomesMichael H Nathanson
Jan 9, 2008·Proceedings of the National Academy of Sciences of the United States of America·Ailan GuoMichael J Comb
Jan 10, 2008·Nature Biotechnology·Mazen W KaramanPatrick P Zarrinkar
Mar 11, 2008·Journal of Proteome Research·Alberto Paradela, Juan Pablo Albar
Aug 5, 2008·Molecular & Cellular Proteomics : MCP·Ulrich KruseCarsten Hopf

❮ Previous
Next ❯

Citations

May 15, 2012·Nature Immunology·Haifa H JabaraRaif S Geha
Apr 17, 2013·Molecular and Cellular Biology·Inmoo RheeAndré Veillette
Jul 20, 2011·Biological Chemistry·Kirstin SandrockBarbara Zieger
Jan 25, 2013·International Journal of Molecular Sciences·Matthew P StokesMichael J Comb
Feb 25, 2015·Brain Research·Malgorzata Ziemka-NaleczTeresa Zalewska
Mar 29, 2014·Biochemical and Biophysical Research Communications·Jinping LuoWilliam H Kinsey
Feb 11, 2014·FEBS Letters·Joell L Solan, Paul D Lampe
Jun 7, 2011·Experimental Cell Research·Colette J ShenChristopher S Chen
Dec 27, 2015·Seminars in Cell & Developmental Biology·Joell L Solan, Paul D Lampe
Jul 22, 2015·Nature Communications·Daniel B GrahamRamnik J Xavier
Aug 23, 2011·Biochimica Et Biophysica Acta·Mehdi Mollapour, Len Neckers
Dec 27, 2016·Journal of Cellular Physiology·Mario GrossiPer Hellstrand
Oct 11, 2016·Integrative Biology : Quantitative Biosciences From Nano to Macro·Andrew W HolleAdam J Engler
Apr 29, 2016·American Journal of Physiology. Cell Physiology·Bong Sook JhunJin O-Uchi
Sep 22, 2017·Pharmacological Reviews·Luc LeybaertRainer Schulz
Jul 28, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Samuel M S Cheung, Hanne L Ostergaard
Dec 9, 2010·Science Signaling·Ariel BensimonYosef Shiloh

❮ Previous
Next ❯

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