{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T10:43:30Z","timestamp":1790246610599,"version":"4.1.0"},"reference-count":43,"publisher":"The Company of Biologists","issue":"12","license":[{"start":{"date-parts":[[2020,9,2]],"date-time":"2020-09-02T00:00:00Z","timestamp":1599004800000},"content-version":"vor","delay-in-days":2904,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,12,15]]},"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>When skin is wounded, migration of epidermal keratinocytes at the wound edge initiates within hours, whereas migration of dermal fibroblasts toward the wounded area remains undetectable until several days later. This \u201ccell type traffic\u201d regulation ensures proper healing of the wound, as disruptions of the regulation could either cause delay of wound healing or result in hypertrophic scars. TGF\u03b23 is the critical traffic controller that selectively halts migration of the dermal, but not epidermal, cells to ensure completion of wound re-epithelialization prior to wound remodeling. However, the mechanism of TGF\u03b23's anti-motility signaling has never been investigated. We report here that activated T\u03b2RII transmits the anti-motility signal of TGF\u03b23 in full to T\u03b2RI, since expression of the constitutively activated T\u03b2RI-TD mutant was sufficient to replace TGF\u03b23 to block PDGF-bb-induced dermal fibroblast migration. Second, the three components of R-Smad complex are all required. Individual downregulation of Smad2, Smad3 or Smad4 prevented TGF\u03b23 from inhibiting dermal fibroblast migration. Third, Protein Kinase Array allowed us to identify the protein kinase A (PKA) as a specific downstream effector of R-Smads in dermal fibroblasts. Activation of PKA alone blocked PDGF-bb-induced dermal fibroblast migration, just like TGF\u03b23. Downregulation of PKA's catalytic subunit nullified the anti-motility signaling of TGF\u03b23. This is the first report on anti-motility signaling mechanism by TGF\u03b2 family cytokines. Significance of this finding is not only limited to wound healing but also to other human disorders, such as heart attack and cancer, where the diseased cells have often managed to avoid the anti-motility effect of TGF\u03b2.<\/jats:p>","DOI":"10.1242\/bio.20122246","type":"journal-article","created":{"date-parts":[[2012,9,28]],"date-time":"2012-09-28T18:51:39Z","timestamp":1348858299000},"page":"1169-1177","source":"Crossref","is-referenced-by-count":19,"title":["The anti-motility signaling mechanism of TGF\u03b23 that controls cell traffic during skin wound healing"],"prefix":"10.1242","volume":"1","author":[{"given":"Arum","family":"Han","sequence":"first","affiliation":[{"name":"The Department of Dermatology and the USC Norris Comprehensive Cancer Center, the University of Southern California Keck School of Medicine, 1441 Eastlake Avenue, Los Angeles, CA 90089, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balaji","family":"Bandyopadhyay","sequence":"additional","affiliation":[{"name":"The Department of Dermatology and the USC Norris Comprehensive Cancer Center, the University of Southern California Keck School of Medicine, 1441 Eastlake Avenue, Los Angeles, CA 90089, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyamvada","family":"Jayaprakash","sequence":"additional","affiliation":[{"name":"The Department of Dermatology and the USC Norris Comprehensive Cancer Center, the University of Southern California Keck School of Medicine, 1441 Eastlake Avenue, Los Angeles, CA 90089, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Lua","sequence":"additional","affiliation":[{"name":"The Department of Dermatology and the USC Norris Comprehensive Cancer Center, the University of Southern California Keck School of Medicine, 1441 Eastlake Avenue, Los Angeles, CA 90089, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Divya","family":"Sahu","sequence":"additional","affiliation":[{"name":"The Department of Dermatology and the USC Norris Comprehensive Cancer Center, the University of Southern California Keck School of Medicine, 1441 Eastlake Avenue, Los Angeles, CA 90089, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Chen","sequence":"additional","affiliation":[{"name":"The Department of Dermatology and the USC Norris Comprehensive Cancer Center, the University of Southern California Keck School of Medicine, 1441 Eastlake Avenue, Los Angeles, CA 90089, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David T.","family":"Woodley","sequence":"additional","affiliation":[{"name":"The Department of Dermatology and the USC Norris Comprehensive Cancer Center, the University of Southern California Keck School of Medicine, 1441 Eastlake Avenue, Los Angeles, CA 90089, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"The Department of Dermatology and the USC Norris Comprehensive Cancer Center, the University of Southern California Keck School of Medicine, 1441 Eastlake Avenue, Los Angeles, CA 90089, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2012,9,20]]},"reference":[{"key":"2021080923284361000_b1","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1016\/0092-8674(77)90057-5","article-title":"The phagokinetic tracks of 3T3 cells.","volume":"11","author":"Albrecht\u2013Buehler","year":"1977","journal-title":"Cell"},{"key":"2021080923284361000_b3","doi-asserted-by":"crossref","first-page":"7155","DOI":"10.1016\/S0021-9258(18)32345-7","article-title":"Transforming growth factor-\u03b2 in human platelets. 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