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The novel adaptor protein Tks4 (SH3PXD2B) is required for functional podosome formation.

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dc.contributor University of Helsinki, Faculty of Pharmacy en
dc.contributor.author Buschman, Matthew D.
dc.contributor.author Bromann, Paul Andrew
dc.contributor.author Cejudo-Martin, Pilar
dc.contributor.author Wen, Fang
dc.contributor.author Pass, Ian
dc.contributor.author Courtneidge, Sara A.
dc.date.accessioned 2012-06-04T08:41:12Z
dc.date.available 2012-06-04T08:41:12Z
dc.date.issued 2009-03
dc.identifier.citation Buschman , M D , Bromann , P A , Cejudo-Martin , P , Wen , F , Pass , I & Courtneidge , S A 2009 , ' The novel adaptor protein Tks4 (SH3PXD2B) is required for functional podosome formation. ' , Molecular Biology of the Cell , vol 20 , no. 5 , pp. 1302-11 . en
dc.identifier.issn 1059-1524
dc.identifier.other PURE: 20814317
dc.identifier.uri http://hdl.handle.net/10138/33910
dc.description.abstract Metastatic cancer cells have the ability to both degrade and migrate through the extracellular matrix (ECM). Invasiveness can be correlated with the presence of dynamic actin-rich membrane structures called podosomes or invadopodia. We showed previously that the adaptor protein tyrosine kinase substrate with five Src homology 3 domains (Tks5)/Fish is required for podosome/invadopodia formation, degradation of ECM, and cancer cell invasion in vivo and in vitro. Here, we describe Tks4, a novel protein that is closely related to Tks5. This protein contains an amino-terminal Phox homology domain, four SH3 domains, and several proline-rich motifs. In Src-transformed fibroblasts, Tks4 is tyrosine phosphorylated and predominantly localized to rosettes of podosomes. We used both short hairpin RNA knockdown and mouse embryo fibroblasts lacking Tks4 to investigate its role in podosome formation. We found that lack of Tks4 resulted in incomplete podosome formation and inhibited ECM degradation. Both phenotypes were rescued by reintroduction of Tks4, whereas only podosome formation, but not ECM degradation, was rescued by overexpression of Tks5. The tyrosine phosphorylation sites of Tks4 were required for efficient rescue. Furthermore, in the absence of Tks4, membrane type-1 matrix metalloproteinase (MT1-MMP) was not recruited to the incomplete podosomes. These findings suggest that Tks4 and Tks5 have overlapping, but not identical, functions, and implicate Tks4 in MT1-MMP recruitment and ECM degradation. en
dc.format.extent 10
dc.language.iso eng
dc.relation.ispartof Molecular Biology of the Cell
dc.relation.uri http://www.ncbi.nlm.nih.gov/pubmed/19144821
dc.subject 1184 Genetics, developmental biology, physiology en
dc.subject CELL ADHESION en
dc.subject CANCER CELL INVASION en
dc.subject 3111 Biomedicine en
dc.subject CANCER METASTASIS en
dc.subject 317 Pharmacy en
dc.subject DRUG TARGET DISCOVERY en
dc.subject 1182 Biochemistry, cell and molecular biology en
dc.title The novel adaptor protein Tks4 (SH3PXD2B) is required for functional podosome formation. en
dc.type A1 Refereed journal article
dc.description.version Peer reviewed
dc.type.dcmitype document
dc.type.uri info:eu-repo/semantics/article
dc.type.uri info:eu-repo/semantics/submittedVersion
dc.contributor.pbl

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