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Here, a new invadopodia synchronization protocol is used to show that the cortactin N-terminal acidic and SH3 domains, involved in Arp2\/3 complex and N-WASP binding and activation, respectively, are both required for invadopodia biogenesis. In addition, through a combination of RNA interference and a wide array of cortactin phosphorylation mutants, we were able to show that three convergent regulatory inputs based on the regulation of cortactin phosphorylation by Src-family kinases, Erk1\/Erk2 and PAK are necessary for invadopodia formation and extracellular matrix degradation. These findings suggest that cortactin is a scaffold protein bringing together the different components necessary for the formation of the invadopodia, and that a fine balance between different phosphorylation events induces subtle changes in structure to calibrate cortactin function.<\/jats:p>","DOI":"10.1242\/jcs.008037","type":"journal-article","created":{"date-parts":[[2008,1,16]],"date-time":"2008-01-16T03:32:31Z","timestamp":1200454351000},"page":"369-378","source":"Crossref","is-referenced-by-count":187,"title":["Multiple regulatory inputs converge on cortactin to control invadopodia biogenesis and extracellular matrix degradation"],"prefix":"10.1242","volume":"121","author":[{"given":"Inmaculada","family":"Ayala","sequence":"first","affiliation":[{"name":"Tumour Cell Invasion Laboratory, Department of Cell Biology and Oncology, Consorzio Mario Negri Sud, S. Maria Imbaro (Chieti), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimiliano","family":"Baldassarre","sequence":"additional","affiliation":[{"name":"Tumour Cell Invasion Laboratory, Department of Cell Biology and Oncology, Consorzio Mario Negri Sud, S. Maria Imbaro (Chieti), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giada","family":"Giacchetti","sequence":"additional","affiliation":[{"name":"Tumour Cell Invasion Laboratory, Department of Cell Biology and Oncology, Consorzio Mario Negri Sud, S. Maria Imbaro (Chieti), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giusi","family":"Caldieri","sequence":"additional","affiliation":[{"name":"Tumour Cell Invasion Laboratory, Department of Cell Biology and Oncology, Consorzio Mario Negri Sud, S. Maria Imbaro (Chieti), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Tete\u0300","sequence":"additional","affiliation":[{"name":"Department of Oral Sciences, University \u201cG. D'Annunzio\u201d, 66013, Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Luini","sequence":"additional","affiliation":[{"name":"Membrane Traffic Laboratory, Department of Cell Biology and Oncology, Consorzio Mario Negri Sud, S. Maria Imbaro (Chieti), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Buccione","sequence":"additional","affiliation":[{"name":"Tumour Cell Invasion Laboratory, Department of Cell Biology and Oncology, Consorzio Mario Negri Sud, S. Maria Imbaro (Chieti), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042701435123300_REF1","doi-asserted-by":"crossref","unstructured":"Artym, V. V., Kindzelskii, A. L., Chen, W. T. and Petty, H. R. (2002). Molecular proximity of seprase and the urokinase-type plasminogen activator receptor on malignant melanoma cell membranes: dependence on beta1 integrins and the cytoskeleton. Carcinogenesis23, 1593-1601.","DOI":"10.1093\/carcin\/23.10.1593"},{"key":"2021042701435123300_REF2","doi-asserted-by":"crossref","unstructured":"Artym, V. V., Zhang, Y., Seillier-Moiseiwitsch, F., Yamada, K. M. and Mueller, S. C. (2006). Dynamic interactions of cortactin and membrane type 1 matrix metalloproteinase at invadopodia: defining the stages of invadopodia formation and function. Cancer Res.66, 3034-3043.","DOI":"10.1158\/0008-5472.CAN-05-2177"},{"key":"2021042701435123300_REF3","doi-asserted-by":"crossref","unstructured":"Balasenthil, S., Sahin, A. A., Barnes, C. J., Wang, R. A., Pestell, R. G., Vadlamudi, R. K. and Kumar, R. (2004). p21-activated kinase-1 signaling mediates cyclin D1 expression in mammary epithelial and cancer cells. J. Biol. 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