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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 Magnusson, M. K. Articles by Dunbar, C. E. Search for Related Content PubMed PubMed Citation Articles by Magnusson, M. K. Articles by Dunbar, C. E. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 October 2001, Vol. 98, No. 8, pp. 2518-2525 NEOPLASIA Rabaptin-5 is a novel fusion partner to platelet-derived growth factor  receptor in chronic myelomonocytic leukemia Magnus K. Magnusson, Kristin E. Meade, Kevin E. Brown, Diane C. Arthur, Lisa A. Krueger, A. John Barrett, and Cynthia E. Dunbar From the Hematology Branch, National Heart, Lung, and Blood Institute, and Laboratory of Pathology, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD. Chromosomal translocations involving the platelet-derived growth factor  receptor (PDGFR) gene have been reported in some patients with chronic myelomonocytic leukemia (CMML). The resultant fusion proteins have constitutive PDGFR tyrosine kinase activity, but the partner genes previously reported (tel, Huntingtin interacting protein 1 [HIP-1], H4/D10S170) have poorly understood roles in the oncogenic activity of the fusion proteins. A novel PDGFR fusion protein has been characterized in a patient with CMML and an acquired t(5;17)(q33;p13). Southern blot analysis on patient leukemia cells demonstrated involvement of the PDGFR gene. Using 5' rapid amplification of complementary DNA ends-polymerase chain reaction (RACE-PCR) on patient RNA, rabaptin-5 was identified as a novel partner fused in-frame to the PDGFR gene. The new fusion protein includes more than 85% of the native Rabaptin-5 fused to the transmembrane and intracellular tyrosine kinase domains of the PDGFR. Transduction with a retroviral vector expressing rabaptin-5/PDGFR transformed the hematopoietic cell line Ba/F3 to growth factor independence and caused a fatal myeloproliferative disease in mice. Rabaptin-5 is a well-studied protein shown to be an essential and rate-limiting component of early endosomal fusion through interaction with the Ras family GTPases Rab5 and Rab4. The fusion protein includes 3 of 4 coiled-coil domains (involved in homodimerization of native rabaptin-5), 2 caspase-3 cleavage sites, and a binding site for the tumor suppressor gene tuberin (tuberous sclerosis complex-2). Early endosomal transport is critical in regulation of various growth factor receptors, through ligand-induced clathrin-mediated endocytosis, and thus this new fusion protein links together 2 important pathways of growth regulation. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. V. Abella and M. Park Breakdown of endocytosis in the oncogenic activation of receptor tyrosine kinases Am J Physiol Endocrinol Metab, May 1, 2009; 296(5): E973 - E984. [Abstract] [Full Text] [PDF] G. Reiterer and A. Yen Platelet-Derived Growth Factor Receptor Regulates Myeloid and Monocytic Differentiation of HL-60 Cells Cancer Res., August 15, 2007; 67(16): 7765 - 7772. [Abstract] [Full Text] [PDF] B. Sargin, C. Choudhary, N. Crosetto, M. H. H. Schmidt, R. Grundler, M. Rensinghoff, C. Thiessen, L. Tickenbrock, J. Schwable, C. Brandts, et al. 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	Copyright © 2001 by American Society of Hematology         Online ISSN: 1528-0020