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Blood, 1 November 2005, Vol. 106, No. 9, pp. 2952-2961. Prepublished online as a Blood First Edition Paper on August 2, 2005; DOI 10.1182/blood-2005-03-1062. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-03-1062v1 106/9/2952    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 Stork, P. J. S. Articles by Dillon, T. J. Search for Related Content PubMed PubMed Citation Articles by Stork, P. J. S. Articles by Dillon, T. J. Related Collections Hematopoiesis and Stem Cells Cell Adhesion and Motility Signal Transduction Free Research Articles Review Articles Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  REVIEW ARTICLES Multiple roles of Rap1 in hematopoietic cells: complementary versus antagonistic functions Philip J. S. Stork, and Tara J. Dillon From the Vollum Institute, Oregon Health & Science University, Portland, OR. Small G proteins serve as critical control points in signal transduction, integrating a wide range of stimuli to dictate discrete cellular outcomes. The outcomes of small G-protein signaling can both potentiate and antagonize one another. Studies in hematopoietic cells have uncovered multiple functions for the small G protein, Rap1 (Ras-proximate-1). Because Rap1 can regulate cell proliferation, differentiation, and adhesion through distinct mechanisms, it serves as a paradigm for the need for tight cellular control of small G-protein function. Rap1 has received recent attention for its role in enhancing integrin-dependent signals. This action of Rap1 augments a variety of processes that characterize hematopoietic-cell function, including aggregation, migration, extravasation, and homing to target tissues. Rap1 may also regulate cellular differentiation and proliferation via pathways that are distinct from those mediating adhesion, and involve regulation of the mitogen-activated protein (MAP) kinase or ERK (extracellular signal-regulated kinase) cascade. These actions of Rap1 occur in selected cell types to enhance or diminish ERK signaling, depending on the expression pattern of the MAP kinase kinase kinases of the Raf family: Raf-1 and B-Raf. This review will examine the functions of Rap1 in hematopoietic cells, and focus on 3 cellular scenarios where the multiple actions of Rap1 function have been proposed. Recent studies implicating Rap1 in the maturation of megakaryocytes, the pathogenesis of chronic myelogenous leukemia (CML), and activation of peripheral T cells will receive particular attention. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. McAvoy, M.-m. Zhou, P. Greengard, and A. C. Nairn Phosphorylation of Rap1GAP, a striatally enriched protein, by protein kinase A controls Rap1 activity and dendritic spine morphology PNAS, March 3, 2009; 106(9): 3531 - 3536. [Abstract] [Full Text] [PDF] L. Xu and M. Komatsu Promoter Cloning and Characterization of the Anti-vascular Proliferation Gene, R-ras: ROLE OF ETS- AND SP-BINDING MOTIFS J. Biol. Chem., January 30, 2009; 284(5): 2706 - 2718. [Abstract] [Full Text] [PDF] R. Verhaar, D. W. 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