Insulin-Like Growth Factor 1 Receptor Signaling Regulates Skin Development and Inhibits Skin Keratinocyte Differentiation
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Published in | Molecular and Cellular Biology Vol. 26; no. 7; pp. 2675 - 2687 |
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AbstractList | The insulin-like growth factor 1 receptor (IGF-1R) is a multifunctional receptor that mediates signals for cell proliferation, differentiation, and survival. Genetic experiments showed that IGF-1R inactivation in skin results in a disrupted epidermis. However, because IGF-1R-null mice die at birth, it is difficult to study the effects of IGF-1R on skin. By using a combined approach of conditional gene ablation and a three-dimensional organotypic model, we demonstrate that IGF-1R-deficient skin cocultures show abnormal maturation and differentiation patterns. Furthermore, IGF-1R-null keratinocytes exhibit accelerated differentiation and decreased proliferation. Investigating the signaling pathway downstream of IGF-1R reveals that insulin receptor substrate 2 (IRS-2) overexpression compensates for the lack of IGF-1R, whereas IRS-1 overexpression does not. We also demonstrate that phosphatidylinositol 3-kinase and extracellular signal-regulated kinase 1 and 2 are involved in the regulation of skin keratinocyte differentiation and take some part in mediating the inhibitory signal of IGF-1R on differentiation. In addition, we show that mammalian target of rapamycin plays a specific role in mediating IGF-1R impedance of action on keratinocyte differentiation. In conclusion, these results reveal that IGF-1R plays an inhibitory role in the regulation of skin development and differentiation. Article Usage Stats Services MCB Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue Spotlights in the Current Issue MCB About MCB Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy MCB RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0270-7306 Online ISSN: 1098-5549 Copyright © 2014 by the American Society for Microbiology. For an alternate route to MCB .asm.org, visit: MCB |
Author | Derek LeRoith Martin Holzenberger Galina Weingarten Dirk Breitkreutz Marianna Sadagurski Efrat Wertheimer Christopher J. Rhodes Shoshana Yakar |
AuthorAffiliation | Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel, 1 Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, 2 INSERM U515, Saint-Antoine Hospital, Paris, France, 3 Pacific Northwest Research Institute, Seattle, Washington, 4 German Cancer Research Center, Division A080, Heidelberg, Germany 5 |
AuthorAffiliation_xml | – name: Department of Pathology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel, 1 Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, 2 INSERM U515, Saint-Antoine Hospital, Paris, France, 3 Pacific Northwest Research Institute, Seattle, Washington, 4 German Cancer Research Center, Division A080, Heidelberg, Germany 5 |
Author_xml | – sequence: 1 givenname: Marianna surname: Sadagurski fullname: Sadagurski, Marianna organization: Department of Pathology, Sackler School of Medicine, Tel Aviv University – sequence: 2 givenname: Shoshana surname: Yakar fullname: Yakar, Shoshana organization: Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health – sequence: 3 givenname: Galina surname: Weingarten fullname: Weingarten, Galina organization: Department of Pathology, Sackler School of Medicine, Tel Aviv University – sequence: 4 givenname: Martin surname: Holzenberger fullname: Holzenberger, Martin organization: INSERM U515, Saint-Antoine Hospital – sequence: 5 givenname: Christopher J. surname: Rhodes fullname: Rhodes, Christopher J. organization: Pacific Northwest Research Institute – sequence: 6 givenname: Dirk surname: Breitkreutz fullname: Breitkreutz, Dirk organization: German Cancer Research Center – sequence: 7 givenname: Derek surname: LeRoith fullname: LeRoith, Derek organization: Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health – sequence: 8 givenname: Efrat surname: Wertheimer fullname: Wertheimer, Efrat email: effy@patholog.tau.ac.il organization: Department of Pathology, Sackler School of Medicine, Tel Aviv University |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/16537911$$D View this record in MEDLINE/PubMed |
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Mendeley... The insulin-like growth factor 1 receptor (IGF-1R) is a multifunctional receptor that mediates signals for cell proliferation, differentiation, and survival.... |
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SubjectTerms | Animals Apoptosis Cell Differentiation - drug effects Cell Proliferation Coculture Techniques Insulin Receptor Substrate Proteins Intracellular Signaling Peptides and Proteins Keratinocytes - cytology Keratinocytes - drug effects Keratinocytes - metabolism Mice Mice, Knockout Mitogen-Activated Protein Kinases - metabolism Models, Biological Oncogene Protein v-akt - metabolism Phosphatidylinositol 3-Kinases - metabolism Phosphoproteins - metabolism Protein Kinases - pharmacology Receptor, IGF Type 1 - deficiency Receptor, IGF Type 1 - metabolism Signal Transduction Skin - cytology Skin - growth & development TOR Serine-Threonine Kinases |
Title | Insulin-Like Growth Factor 1 Receptor Signaling Regulates Skin Development and Inhibits Skin Keratinocyte Differentiation |
URI | http://mcb.asm.org/content/26/7/2675.abstract https://www.tandfonline.com/doi/abs/10.1128/MCB.26.7.2675-2687.2006 https://www.ncbi.nlm.nih.gov/pubmed/16537911 https://search.proquest.com/docview/17093118 https://search.proquest.com/docview/67757482 https://pubmed.ncbi.nlm.nih.gov/PMC1430337 |
Volume | 26 |
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