{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T12:03:23Z","timestamp":1791029003740,"version":"4.1.0"},"reference-count":38,"publisher":"The Company of Biologists","issue":"1","license":[{"start":{"date-parts":[[2001,1,1]],"date-time":"2001-01-01T00:00:00Z","timestamp":978307200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2001,1,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>The non-receptor tyrosine kinase Src was shown to be essential for osteoclast function in vivo. We have previously reported that engagement of \u03b1v\u03b23 integrin in osteoclasts induces tyrosine phosphorylation and activation of the adhesion kinase PYK2 and the adaptor protein p130Cas in a Src-dependent manner. The objective of this study was to analyse the role of c-Src in the \u03b1v\u03b23 integrin-dependent recruitment of signalling and cytoskeletal molecules in osteoclasts during bone resorption. Using prefusion osteoclasts (pOCs) obtained from cocultures of osteoblasts and spleen cells isolated from Src\u2212\/\u2212 mice or their normal littermates, we found: (1) similar expression levels and ligand binding affinities of \u03b1v\u03b23 integrins in Src\u2212\/\u2212 and Src+\/? pOCs, (2) reduced adhesion and spreading of Src\u2212\/\u2212 pOCs, (3) defective organisation of the microfilament proteins, F-actin, vinculin and paxillin, and of PYK2 and p130Cas in the sealing zone of Src\u2212\/\u2212 OCLs, and (4) hyperclustering of \u03b1v\u03b23 integrins together with microfilament and signalling proteins in the basal membrane of Src-deficient OCLs. In normal OCLs, the tyrosine kinase inhibitor tyrphostin A9 inhibits actin ring formation, bone resorption and tyrosine phosphorylation of several proteins, including c-Src. Furthermore, tyrphostin A9 induced similar hyperclustering of \u03b1v\u03b23 integrins in osteoclasts as observed in Src\u2212\/\u2212 OCLs. Taken together, these findings suggest that normal localisation of \u03b1v\u03b23 and recruitment of its downstream effectors to the appropriate compartments of the osteoclast during resorption depend on Src kinase activity.<\/jats:p>","DOI":"10.1242\/jcs.114.1.149","type":"journal-article","created":{"date-parts":[[2021,4,25]],"date-time":"2021-04-25T18:40:37Z","timestamp":1619376037000},"page":"149-160","source":"Crossref","is-referenced-by-count":50,"title":["Abnormal localisation and hyperclustering of \u03b1V\u03b23 integrins and associated proteins in Src-deficient or tyrphostin A9-treated osteoclasts"],"prefix":"10.1242","volume":"114","author":[{"given":"P. T.","family":"Lakkakorpi","sequence":"first","affiliation":[{"name":"1 Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA"},{"name":"2 Institute of Biomedicine, Department of Anatomy, University of Turku, Kiinamyllynkatu 10, FIN-20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Nakamura","sequence":"additional","affiliation":[{"name":"1 Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Young","sequence":"additional","affiliation":[{"name":"1 Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Lipfert","sequence":"additional","affiliation":[{"name":"1 Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. A.","family":"Rodan","sequence":"additional","affiliation":[{"name":"1 Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. T.","family":"Duong","sequence":"additional","affiliation":[{"name":"1 Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2001,1,1]]},"reference":[{"key":"2024011500314450700_JOCES_114_1_149C1","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1172\/JCI116032","article-title":"Requirement of pp60c-src expression for osteoclasts to form ruffled borders and resorb bone in mice","volume":"90","author":"Boyce","year":"1992","journal-title":"J. Clin. 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