SRC catalytic but not scaffolding function is needed for integrin-regulated tyrosine phosphorylation, cell migration, and cell spreading.

Molecular and Cellular Biology
L A CaryJ A Cooper

Abstract

Src family kinases (SFKs) are crucial for signaling through a variety of cell surface receptors, including integrins. There is evidence that integrin activation induces focal adhesion kinase (FAK) autophosphorylation at Y397 and that Src binds to and is activated by FAK to carry out subsequent phosphorylation events. However, it has also been suggested that Src functions as a scaffolding molecule through its SH2 and SH3 domains and that its kinase activity is not necessary. To examine the role of SFKs in integrin signaling, we have expressed various Src molecules in fibroblasts lacking other SFKs. In cells plated on fibronectin, FAK could indeed autophosphorylate at Y397 independently of Src but with lower efficiency than when Src was present. This step was promoted by kinase-inactive Src, but Src kinase activity was required for full rescue. Src kinase activity was also required for phosphorylation of additional sites on FAK and for other integrin-directed functions, including cell migration and spreading on fibronectin. In contrast, Src mutations in the SH2 or SH3 domain greatly reduced binding to FAK, Cas, and paxillin but had little effect on tyrosine phosphorylation or biological assays. Furthermore, our indirect evidence ...Continue Reading

References

Jul 1, 1992·The Journal of Cell Biology·K B KaplanD O Morgan
Oct 1, 1988·Molecular and Cellular Biology·T E KmiecikD Shalloway
Oct 13, 1995·Biochemical and Biophysical Research Communications·S KanazawaS Aizawa
Mar 1, 1994·Molecular and Cellular Biology·M D SchallerJ T Parsons
Aug 1, 1994·Molecular and Cellular Biology·B W Howell, J A Cooper
Feb 28, 1995·Proceedings of the National Academy of Sciences of the United States of America·J DuysterJ Y Wang
Jul 14, 1995·The Journal of Biological Chemistry·H C ChenJ L Guan
Sep 1, 1995·The Journal of Cell Biology·M D SchallerJ T Parsons
Feb 1, 1996·Experimental Cell Research·D IlićS Aizawa
Mar 8, 1996·The Journal of Biological Chemistry·H KawakatsuJ Yano
Jun 7, 1996·Biochimica Et Biophysica Acta·M T Brown, J A Cooper
Jan 1, 1995·Annual Review of Cell and Developmental Biology·M A SchwartzM H Ginsberg
Feb 7, 1998·The Journal of Biological Chemistry·J W ThomasM D Schaller
Feb 14, 1998·The Journal of Cell Biology·L A CaryJ L Guan
Jan 22, 1998·Current Opinion in Structural Biology·F Sicheri, J Kuriyan
Jan 1, 1997·Annual Review of Cell and Developmental Biology·S M Thomas, J S Brugge
Mar 21, 1998·The Journal of Cell Biology·R L KlemkeD A Cheresh
Apr 23, 1999·The Journal of Biological Chemistry·H R ReiskeH C Chen
May 6, 1999·The EMBO Journal·R A KlinghofferP Soriano
Jun 4, 1999·Progress in Biophysics and Molecular Biology·D D SchlaepferD J Sieg
Aug 4, 1999·Proceedings of the National Academy of Sciences of the United States of America·X ZhangS K Hanks
Aug 14, 1999·Science·F G Giancotti, E Ruoslahti

❮ Previous
Next ❯

Citations

Nov 27, 2009·The Journal of Biological Chemistry·Natasha R SchuhAmy H Bouton
May 29, 2010·The Journal of Biological Chemistry·Nicole TegtmeyerSteffen Backert
Sep 29, 2011·The Journal of Biological Chemistry·Alessandro PrinettiSandro Sonnino
Apr 5, 2008·The Journal of Biological Chemistry·Vitalyi O RybinSusan F Steinberg
Jan 14, 2005·Molecular Biology of the Cell·J SrivastavaM Arpin
Jul 21, 2006·Molecular Biology of the Cell·Michael A Partridge, Eugene E Marcantonio
Oct 23, 2002·Molecular and Cellular Biology·Madeleine ToutantJean-Antoine Girault
Jun 1, 2004·Molecular and Cellular Biology·Jill M DuntyMichael D Schaller
Oct 23, 2003·Annual Review of Cell and Developmental Biology·Filippo G Giancotti, Guido Tarone
Apr 22, 2011·American Journal of Physiology. Cell Physiology·Justine ElliottPatricia D Wilson
Dec 8, 2010·Cancer Research·Houjian CaiOwen N Witte
Sep 17, 2008·BMC Cell Biology·Alok Sharma, Bruce J Mayer
Jun 27, 2009·Journal of Atherosclerosis and Thrombosis·Nwe Nwe SoeMasao Yoshizumi
Dec 3, 2003·Proceedings of the National Academy of Sciences of the United States of America·Takaki ShimaMasato Okada
Dec 16, 2004·Proceedings of the National Academy of Sciences of the United States of America·Toshinori IwaharaHidesaburo Hanafusa
Apr 28, 2004·Current Opinion in Genetics & Development·David D Schlaepfer, Satyajit K Mitra
Jun 15, 2011·Nature Chemical Biology·Akash GulyaniKlaus M Hahn
Aug 23, 2011·Cellular and Molecular Bioengineering·Jihye SeongYingxiao Wang
Apr 25, 2012·The Journal of Cell Biology·Jeanine PignatelliChristopher E Turner
Aug 19, 2007·The Journal of Cell Biology·Dmitry E ShvartsmanYoav I Henis
Oct 4, 2006·The Journal of Cell Biology·Mara FornaroAnton M Bennett
Mar 5, 2003·The Journal of Cell Biology·Datsun A HsiaDavid D Schlaepfer
Dec 20, 2011·European Journal of Cell Biology·Verena NiediekBernd Hoffmann
Aug 19, 2006·The Journal of Investigative Dermatology·David P ChomaC Michael DiPersio
Oct 22, 2008·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Janka TeutschbeinSvenja Meierjohann
Jan 29, 2010·Molecular Reproduction and Development·Michelle F Goody, Clarissa A Henry
Dec 30, 2014·Fundamental & Clinical Pharmacology·Amit KumarNirmal Singh
Aug 11, 2015·The FEBS Journal·Hiroaki MachiyamaHideaki Fujita
Nov 10, 2004·Medical Hypotheses·Jian-Guo RenConover Talbot
Nov 25, 2004·Experimental Cell Research·Silvia ContinoloGiorgio Berton
May 8, 2004·Trends in Cell Biology·Neil O Carragher, Margaret C Frame
Mar 11, 2006·Experimental Cell Research·Agnes G S H van RossumEd Schuuring

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