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Using GTP analogues, phosphoinositides, a phosphoinositide-binding peptide, constitutively active or inactive Rho GTPase mutants, and activating or inhibitory peptides derived from neural Wiskott-Aldrich syndrome family proteins (N-WASP), we identified signaling pathways leading from the FMLP receptor to actin nucleation that require Cdc42, but then diverge. One branch traverses the actin nucleation pathway involving N-WASP and the Arp2\/3 complex, whereas the other operates through active Rac to promote actin nucleation. Both pathways depend on phosphoinositide expression. Since maximal inhibition of the Arp2\/3 pathway leaves an N17Rac inhibitable alternate pathway intact, we conclude that this alternate involves phosphoinositide-mediated uncapping of actin filament barbed ends.<\/jats:p>","DOI":"10.1083\/jcb.150.4.785","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:45:41Z","timestamp":1027701941000},"page":"785-796","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":88,"title":["Two Pathways through Cdc42 Couple the <i>N<\/i>-Formyl Receptor to Actin Nucleation in Permeabilized Human Neutrophils"],"prefix":"10.1083","volume":"150","author":[{"given":"M.","family":"Glogauer","sequence":"first","affiliation":[{"name":"aHematology Division, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Hartwig","sequence":"additional","affiliation":[{"name":"aHematology Division, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Stossel","sequence":"additional","affiliation":[{"name":"aHematology Division, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2000,8,21]]},"reference":[{"key":"2023072902321435700_Akasakietal1999","doi-asserted-by":"crossref","first-page":"18055","DOI":"10.1074\/jbc.274.25.18055","article-title":"Phosphoinositide 3-kinase-dependent and -independent activation of the small GTPase Rac2 in human neutrophils","volume":"274","author":"Akasaki","year":"1999","journal-title":"J. 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