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This Article Full Text Full Text (PDF) 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 Zutter, M. M. Articles by Yang, X. Search for Related Content PubMed PubMed Citation Articles by Zutter, M. M. Articles by Yang, X. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, Vol. 93 No. 5 (March 1), 1999: pp. 1600-1611 The Megakaryocyte/Platelet-Specific Enhancer of the 21 Integrin Gene: Two Tandem AP1 Sites and the Mitogen-Activated Protein Kinase Signaling Cascade Mary M. Zutter, Audrey D. Painter, and Xun Yang From the Department of Pathology, Washington University School of Medicine, St Louis, MO. The 21 integrin, a collagen receptor on platelets and megakaryocytes, is required for normal platelet function. Transcriptional regulation of the 2 integrin gene in cells undergoing megakaryocytic differentiation requires a core promoter between bp 30 and 92, a silencer between bp 92 and 351, and megakaryocytic enhancers in the distal 5' flank. We have now identified a 229-bp region of the distal 5' flank of the 2 integrin gene required for high-level enhancer activity in cells with megakaryocytic features. Two tandem AP1 binding sites with dyad symmetry are required for enhancer activity and for DNA-protein complex formation with members of the c-fos/c-jun family. The requirement for AP1 activation suggested a role for the mitogen-activated protein kinase (MAPK) signaling pathway in regulating 2 integrin gene expression. Inhibition of the MAP kinase cascade with PD98059, a specific inhibitor of MAPK kinase 1, prevented the expression of the 2 integrin subunit in cells induced to become megakaryocytic. We provide a model of megakaryocytic differentiation in which expression of the 2 integrin gene requires signaling via the MAP kinase pathway to activate two tandem AP1 binding sites in the 2 integrin enhancer. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. Tanaka, T. Owaki, S. Kamiya, T. Matsunaga, K. Shimoda, H. Kodama, R. Hayashi, T. Abe, Y. P. Harada, M. Shimonaka, et al. VLA-5-mediated Adhesion to Fibronectin Accelerates Hemin-stimulated Erythroid Differentiation of K562 Cells through Induction of VLA-4 Expression J. Biol. Chem., July 24, 2009; 284(30): 19817 - 19825. [Abstract] [Full Text] [PDF] P. Halasz, G. Holloway, S. J. Turner, and B. S. 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