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Blood, 1 July 2008, Vol. 112, No. 1, pp. 100-110. Prepublished online as a Blood First Edition Paper on March 12, 2008; DOI 10.1182/blood-2007-07-104455. This Article Full Text (PDF) Supplemental Figures and Videos All Versions of this Article: blood-2007-07-104455v1 112/1/100    most recent Alert me when this article is cited Alert me if a correction is posted 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 Stepanova, V. Articles by Cines, D. B. Search for Related Content PubMed PubMed Citation Articles by Stepanova, V. Articles by Cines, D. B. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 31, 2007 Accepted February 1, 2008 Nuclear translocation of urokinase-type plasminogen activator Victoria Stepanova*, Tatiana Lebedeva, Alice Kuo, Serge Yarovoi, Sergei Tkachuk, Sergei Zaitsev, Khalil Bdeir, Inna Dumler, Michael S. Marks, Yelena Parfyonova, Vsevolod A. Tkachuk, Abd Al-Roof Higazi, and Douglas B. Cines Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, United States Department of Nephrology, Hannover Medical School, Hannover, Germany Department of Pharmacology, University of Pennsylvania, Philadelphia, PA, United States Biochemistry, Russian Cardiology Research Center, Moscow, Russian Federation Department of Clinical Biochemistry, Hadassah University Hospital and Hebre University-Hadassah Medical School, Jerusalem, Israel * Corresponding author; email: vstepano{at}mail.med.upenn.edu. Urokinase-type plasminogen activator (uPA) participates in diverse (patho)physiological processes through intracellular signaling events that affect cell adhesion, migration and proliferation, although the mechanisms by which these occur are only partially understood. Here we report that upon cell binding and internalization, single-chain uPA (scuPA) translocates to the nucleus within minutes. Nuclear translocation does not involve proteolytic activation or degradation of scuPA. Neither urokinase receptor (uPAR) nor the low-density lipoprotein-related receptor (LRP) are required for nuclear targeting. Rather, translocation involves the binding of scuPA to the nucleocytoplasmic shuttle protein nucleolin through a region containing the kringle domain. RNA interference and mutational analysis demonstrate that nucleolin is required for the nuclear transport of scuPA. Furthermore, nucleolin is required for the induction smooth muscle -actin (-SMA) by scuPA. These data reveal a novel pathway by which uPA is rapidly translocated to the nucleus where it might participate in regulating gene expression. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Urokinase: the identity crisis continues Steven L. Gonias Blood 2008 112: 8. [Full Text] [PDF] This article has been cited by other articles: R. N. Re and J. L. Cook Senescence, apoptosis, and stem cell biology: the rationale for an expanded view of intracrine action Am J Physiol Heart Circ Physiol, September 1, 2009; 297(3): H893 - H901. [Abstract] [Full Text] [PDF] R. A. Mesa How I treat symptomatic splenomegaly in patients with myelofibrosis Blood, May 28, 2009; 113(22): 5394 - 5400. [Abstract] [Full Text] [PDF]

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