{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T06:56:41Z","timestamp":1788245801687,"version":"build-2803163510"},"reference-count":43,"publisher":"Portland Press Ltd.","issue":"1","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2006,7,1]]},"abstract":"<jats:p>The Rac-specific GEF (guanine-nucleotide exchange factor) Tiam1 (T-lymphoma invasion and metastasis 1) regulates migration, cell\u2013matrix and cell\u2013cell adhesion by modulating the actin cytoskeleton through the GTPase, Rac1. Using yeast two-hybrid screening and biochemical assays, we found that Tiam1 interacts with the p21-Arc [Arp (actin-related protein) complex] subunit of the Arp2\/3 complex. Association occurred through the N-terminal pleckstrin homology domain and the adjacent coiled-coil region of Tiam1. As a result, Tiam1 co-localizes with the Arp2\/3 complex at sites of actin polymerization, such as epithelial cell\u2013cell contacts and membrane ruffles. Deletion of the p21-Arc-binding domain in Tiam1 impairs its subcellular localization and capacity to activate Rac1, suggesting that binding to the Arp2\/3 complex is important for the function of Tiam1. Indeed, blocking Arp2\/3 activation with a WASP (Wiskott\u2013Aldrich syndrome protein) inhibitor leads to subcellular relocalization of Tiam1 and decreased Rac activation. Conversely, functionally active Tiam1, but not a GEF-deficient mutant, promotes activation of the Arp2\/3 complex and its association with cytoskeletal components, indicating that Tiam1 and Arp2\/3 are mutually dependent for their correct localization and signalling. Our data suggests a model in which the Arp2\/3 complex acts as a scaffold to localize Tiam1, and thereby Rac activity, which are both required for activation of the Arp2\/3 complex and further Arp2\/3 recruitment. This \u2018self-amplifying\u2019 signalling module involving Tiam1, Rac and the Arp2\/3 complex could thus drive actin polymerization at specific sites in cells that are required for dynamic morphological changes.<\/jats:p>","DOI":"10.1042\/bj20051957","type":"journal-article","created":{"date-parts":[[2006,6,16]],"date-time":"2006-06-16T12:03:41Z","timestamp":1150459421000},"page":"39-45","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Interaction between Tiam1 and the Arp2\/3 complex links activation of Rac to actin polymerization"],"prefix":"10.1042","volume":"397","author":[{"given":"Jean\u00a0Paul","family":"ten\u00a0Klooster","sequence":"first","affiliation":[{"name":"The Netherlands Cancer Institute, Division of Cell Biology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva\u00a0E.","family":"Evers","sequence":"additional","affiliation":[{"name":"The Netherlands Cancer Institute, Division of Cell Biology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lennert","family":"Janssen","sequence":"additional","affiliation":[{"name":"The Netherlands Cancer Institute, Division of Cell Biology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura\u00a0M.","family":"Machesky","sequence":"additional","affiliation":[{"name":"Division of Molecular Cell Biology, School of Biosciences, University of Birmingham, Birmingham B15 2TT, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frits","family":"Michiels","sequence":"additional","affiliation":[{"name":"The Netherlands Cancer Institute, Division of Cell Biology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Hordijk","sequence":"additional","affiliation":[{"name":"Sanquin Research and Landsteiner Laboratorium, Academic Medical Center, University of Amsterdam, Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John\u00a0G.","family":"Collard","sequence":"additional","affiliation":[{"name":"The Netherlands Cancer Institute, Division of Cell Biology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2006,6,14]]},"reference":[{"key":"2021112213123650400_B1","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1126\/science.279.5350.509","article-title":"Rho GTPases and the actin cytoskeleton","volume":"279","author":"Hall","year":"1998","journal-title":"Science"},{"key":"2021112213123650400_B2","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1038\/354311a0","article-title":"Catalysis of guanine nucleotide exchange on the CDC42Hs protein by the dbl oncogene product","volume":"354","author":"Hart","year":"1991","journal-title":"Nature (London)"},{"key":"2021112213123650400_B3","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S1097-2765(00)80019-2","article-title":"PAK kinases are directly coupled to the PIX family of nucleotide exchange factors","volume":"1","author":"Manser","year":"1998","journal-title":"Mol. 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