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Blood, 1 March 2008, Vol. 111, No. 5, pp. 2647-2656. Prepublished online as a Blood First Edition Paper on November 9, 2007; DOI 10.1182/blood-2007-08-109710. This Article Full Text Full Text (PDF) Supplemental Methods and Figure All Versions of this Article: blood-2007-08-109710v1 111/5/2647    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Chrzanowska-Wodnicka, M. Articles by VanSluys, J. Search for Related Content PubMed PubMed Citation Articles by Chrzanowska-Wodnicka, M. Articles by VanSluys, J. Related Collections Hemostasis, Thrombosis, and Vascular Biology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Defective angiogenesis, endothelial migration, proliferation, and MAPK signaling in Rap1b-deficient mice Magdalena Chrzanowska-Wodnicka1, Anna E. Kraus2, Daniel Gale1, Gilbert C. White, II1, and Jillian VanSluys1 1 Blood Research Institute, BloodCenter of Wisconsin, Milwaukee; and 2 Department of Medicine and Carolina Cardiovascular Biology Center, University of North Carolina at Chapel Hill Angiogenesis is the main mechanism of vascular remodeling during late development and, after birth, in wound healing. Perturbations of angiogenesis occur in cancer, diabetes, ischemia, and inflammation. While much progress has been made in identifying factors that control angiogenesis, the understanding of the precise molecular mechanisms involved is incomplete. Here we identify a small GTPase, Rap1b, as a positive regulator of angiogenesis. Rap1b-deficient mice had a decreased level of Matrigel plug and neonatal retinal neovascularization, and aortas isolated from Rap1b-deficient animals had a reduced microvessel sprouting response to 2 major physiological regulators of angiogenesis: vascular endothelial growth factor (VEGF) and basic fibroblasts growth factor (bFGF), indicating an intrinsic defect in endothelial cells. Proliferation of retinal endothelial cells in situ and in vitro migration of lung endothelial cells isolated from Rap1b-deficient mice were inhibited. At the molecular level, activation of 2 MAP kinases, p38 MAPK and p42/44 ERK, important regulators of endothelial migration and proliferation, was decreased in Rap1b-deficient endothelial cells in response to VEGF stimulation. These studies provide evidence that Rap1b is required for normal angiogenesis and reveal a novel role of Rap1 in regulation of proangiogenic signaling in endothelial cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Rap1B speeds up angiogenesis Fried J. T. Zwartkruis and Johannes L. Bos Blood 2008 111: 2500-2501. [Full Text] [PDF] This article has been cited by other articles: A. C. Roman, J. M. Carvajal-Gonzalez, E. M. Rico-Leo, and P. M. Fernandez-Salguero Dioxin Receptor Deficiency Impairs Angiogenesis by a Mechanism Involving VEGF-A Depletion in the Endothelium and Transforming Growth Factor-{beta} Overexpression in the Stroma J. Biol. 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Sanders Hematopoietic Protein Tyrosine Phosphatase Mediates {beta}2-Adrenergic Receptor-Induced Regulation of p38 Mitogen-Activated Protein Kinase in B Lymphocytes Mol. Cell. Biol., February 1, 2009; 29(3): 675 - 686. [Abstract] [Full Text] [PDF] G. Carmona, S. Gottig, A. Orlandi, J. Scheele, T. Bauerle, M. Jugold, F. Kiessling, R. Henschler, A. M. Zeiher, S. Dimmeler, et al. Role of the small GTPase Rap1 for integrin activity regulation in endothelial cells and angiogenesis Blood, January 8, 2009; 113(2): 488 - 497. [Abstract] [Full Text] [PDF] Y. Chen, M. Yu, A. Podd, R. Wen, M. Chrzanowska-Wodnicka, G. C. White, and D. Wang A critical role of Rap1b in B-cell trafficking and marginal zone B-cell development Blood, May 1, 2008; 111(9): 4627 - 4636. [Abstract] [Full Text] [PDF] U. Fischer, A. Keller, P. Leidinger, S. Deutscher, S. Heisel, S. Urbschat, H.-P. Lenhof, and E. 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