{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:29:06Z","timestamp":1790753346261,"version":"4.1.0"},"reference-count":53,"publisher":"The Company of Biologists","issue":"11","license":[{"start":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T00:00:00Z","timestamp":1590969600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"funder":[{"name":"Research Grant Council of Hong Kong","award":["27110615"],"award-info":[{"award-number":["27110615"]}]},{"name":"Research Grant Council of Hong Kong","award":["17124117"],"award-info":[{"award-number":["17124117"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,6,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Podosomes play crucial roles in macrophage adhesion and migration. Wiskott\u2013Aldrich syndrome protein (WASP; also known as WAS)-mediated actin polymerization is one of the key events initiating podosome formation. Nevertheless, membrane signals to trigger WASP activation at macrophage podosomes remain unclear. Here, we show that phosphatidylinositol (3,4,5)-trisphosphate [PI(3,4,5)P3] lipids are enriched at the podosome and stably recruit WASP rather than the WASP-5KE mutant. Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit \u03b2 (PIK3CB) is spatially located at the podosome core. Inhibition of PIK3CB and overexpression of phosphatase and tensin homolog (PTEN) impede F-actin polymerization of the podosome. PIK3CB activation is regulated by Abl1 and Src family kinases. At the podosome core, Src and Hck promote the phosphorylation of Tyr488 in the consensus Y-x-x-M motif of Abl1, which enables the association of phosphoinositide 3-kinase (PI3K) regulatory subunits. Knockdown of Abl1 rather than Abl2 suppresses the PI3K\/Akt pathway, regardless of Src and Hck activities. Reintroduction of wild-type Abl1 rather than the Abl1-Y488F mutant rescues PI3KR1 recruitment and PI3K activation. When PIK3CB, Abl1 or Src\/Hck is suppressed, macrophage podosome formation, matrix degradation and chemotactic migration are inhibited. Thus, Src\/Hck-mediated phosphorylation of Abl1 Tyr488 triggers PIK3CB-dependent PI(3,4,5)P3 production and orchestrates the assembly and function of macrophage podosomes.<\/jats:p>","DOI":"10.1242\/jcs.234385","type":"journal-article","created":{"date-parts":[[2020,5,11]],"date-time":"2020-05-11T20:14:34Z","timestamp":1589228074000},"source":"Crossref","is-referenced-by-count":26,"title":["Abl-mediated PI3K activation regulates macrophage podosome formation"],"prefix":"10.1242","volume":"133","author":[{"given":"Yuhuan","family":"Zhou","sequence":"first","affiliation":[{"name":"School of Biomedical Sciences, Faculty of Medicine, University of Hong Kong , Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Feng","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Faculty of Medicine, University of Hong Kong , Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fakun","family":"Cao","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Faculty of Medicine, University of Hong Kong , Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoting","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Faculty of Medicine, University of Hong Kong , Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojie","family":"Xia","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Faculty of Medicine, University of Hong Kong , Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8821-8877","authenticated-orcid":false,"given":"Cheng-han","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Faculty of Medicine, University of Hong Kong , Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2020,6,8]]},"reference":[{"key":"2024061318484852600_JCS234385C1","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1038\/ncb3286","article-title":"Isoform diversity in the Arp2\/3 complex determines actin filament dynamics","volume":"18","author":"Abella","year":"2016","journal-title":"Nat. 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