SEARCH:   Advanced

Blood, 15 November 2004, Vol. 104, No. 10, pp. 3161-3168. Prepublished online as a Blood First Edition Paper on July 22, 2004; DOI 10.1182/blood-2004-03-0893. This Article Full Text (PDF) All Versions of this Article: 2004-03-0893v1 104/10/3161    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 Kanaji, T. Articles by Ware, J. Search for Related Content PubMed PubMed Citation Articles by Kanaji, T. Articles by Ware, J. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 12, 2004 Accepted June 27, 2004 Megakaryocyte proliferation and ploidy regulated by the cytoplasmic tail of glycoprotein Ib Taisuke Kanaji, Susan Russell, Janet Cunningham, Izuhara Kenji, Joan E Fox, and Jerry Ware* Department of Molecular and Experimental Medicine, Roon Research Center for Arteriosclerosis and Thrombosis, Division of Experimental Hemostasis and Thrombosis, La Jolla, CA, USA; Department of Biomolecular Sciences, Saga Medical School, Nabeshima, Saga, Japan Department of Molecular and Experimental Medicine, Roon Research Center for Arteriosclerosis and Thrombosis, Division of Experimental Hemostasis and Thrombosis, La Jolla, CA, USA Department of Molecular Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, The Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH, USA Department of Biomolecular Sciences, Saga Medical School, Nabeshima, Saga, Japan * Corresponding author; email: jware{at}scripps.edu. We have investigated the ability of glycoprotein (GP) Ib, a megakaryocytic gene product, to sequester the signal transduction protein, 14-3-3, and influence megakaryocytopoiesis. Utilizing a Gp1ba(-/-) mouse colony, we compare the rescued phenotypes produced by a wild-type human GP Ib allele or a similar allele containing a 6-residue cytoplasmic tail truncation that abrogates binding to 14-3-3. The observed phenotypes illustrate an involvement for GP Ib in thrombopoietin-mediated events of megakaryocyte proliferation, polyploidization, and the expression of apoptotic markers in maturing megakaryocytes. A hypothesis is developed for the involvement of a GP Ib/14-3-3/PI-3 kinase complex in regulating thrombopoietin-mediated responses. An observed increase in thrombopoietin-mediated Akt phosphorylation in the truncated variant supports the hypothesis and leads to a development of a model where the GP Ib cytoplasmic tail sequesters signaling proteins during megakaryocytopoiesis and, as such, becomes a critical regulator in the temporal sequence of events that lead to normal megakaryocyte maturation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: A tail with a leading role in megakaryocytes: the glycoprotein Ib Katya Ravid Blood 2004 104: 3004-3005. [Full Text] [PDF] This article has been cited by other articles: C. Strassel, A. Eckly, C. Leon, C. Petitjean, M. Freund, J.-P. Cazenave, C. Gachet, and F. Lanza Intrinsic impaired proplatelet formation and microtubule coil assembly of megakaryocytes in a mouse model of Bernard-Soulier syndrome Haematologica, June 1, 2009; 94(6): 800 - 810. [Abstract] [Full Text] [PDF] Y. Li, J. Lu, and E. V. Prochownik Modularity of the Oncoprotein-like Properties of Platelet Glycoprotein Ib{alpha} J. Biol. Chem., January 16, 2009; 284(3): 1410 - 1418. [Abstract] [Full Text] [PDF] F.-T. Mu, R. K. Andrews, J. F. Arthur, A. D. Munday, S. L. Cranmer, S. P. Jackson, F. C. Stomski, A. F. Lopez, and M. C. Berndt A functional 14-3-3{zeta}-independent association of PI3-kinase with glycoprotein Ib{alpha}, the major ligand-binding subunit of the platelet glycoprotein Ib-IX-V complex Blood, May 1, 2008; 111(9): 4580 - 4587. [Abstract] [Full Text] [PDF] M. Iannacone, G. Sitia, M. Isogawa, J. K. Whitmire, P. Marchese, F. V. Chisari, Z. M. Ruggeri, and L. G. Guidotti Platelets prevent IFN-{alpha}/ -induced lethal hemorrhage promoting CTL-dependent clearance of lymphocytic choriomeningitis virus PNAS, January 15, 2008; 105(2): 629 - 634. [Abstract] [Full Text] [PDF] S. Jain, M. Zuka, J. Liu, S. Russell, J. Dent, J. A. Guerrero, J. Forsyth, B. Maruszak, T. K. Gartner, B. Felding-Habermann, et al. Platelet glycoprotein Ib{alpha} supports experimental lung metastasis PNAS, May 22, 2007; 104(21): 9024 - 9028. [Abstract] [Full Text] [PDF] Y. Li, J. Lu, and E. V. Prochownik c-Myc-mediated genomic instability proceeds via a megakaryocytic endomitosis pathway involving Gp1b{alpha} PNAS, February 27, 2007; 104(9): 3490 - 3495. [Abstract] [Full Text] [PDF] R. Guerriero, I. Parolini, U. Testa, P. Samoggia, E. Petrucci, M. Sargiacomo, C. Chelucci, M. Gabbianelli, and C. Peschle Inhibition of TPO-induced MEK or mTOR activity induces opposite effects on the ploidy of human differentiating megakaryocytes J. Cell Sci., February 15, 2006; 119(4): 744 - 752. [Abstract] [Full Text] [PDF]

	Copyright © 2004 by American Society of Hematology         Online ISSN: 1528-0020