Journal article
Nck adaptor proteins link Tks5 to invadopodia actin regulation and ECM degradation
SS Stylli, TTI Stacey, AM Verhagen, SS Xu, I Pass, SA Courtneidge, P Lock
Journal of Cell Science | COMPANY BIOLOGISTS LTD | Published : 2009
DOI: 10.1242/jcs.046680
Abstract
Invadopodia are actin-based projections enriched with proteases, which invasive cancer cells use to degrade the extracellular matrix (ECM). The Phox homology (PX)-Src homology (SH)3 domain adaptor protein Tks5 (also known as SH3PXD2A) cooperates with Src tyrosine kinase to promote invadopodia formation but the underlying pathway is not clear. Here we show that Src phosphorylates Tks5 at Y557, inducing it to associate directly with the SH3-SH2 domain adaptor proteins Nck1 and Nck2 in invadopodia. Tks5 mutants unable to bind Nck show reduced matrix degradation-promoting activity and recruit actin to invadopodia inefficiently. Conversely, Src- and Tks5-driven matrix proteolysis and actin assemb..
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Awarded by National Cancer Institute
Funding Acknowledgements
We thank Stephen Cody for confocal microscopy advice and training, Darren Seals for protocols to prepare labelled gelatin coverslips, Brian Seed, Ulrike Novak, Nathan Godde and Phil Darcy for plasmids and cell lines. This work was supported by grants from the NHMRC ( Australia), the National Cancer Institute of the USA (NIH) and the John T. Reid Charitable Trusts. Deposited in PMC for release after 12 months.