Effects of inhibitor of Src kinases, SU6656, on differentiation of megakaryocytic progenitors and activity of α1,6-fucosyltransferase
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α1,6-fucosyltransferase (FUT8) attaches fucose residues via an α1,6 linkage to the innermost N-acetylglucosamine residue of N-linked glycans. Glycans with this type of structure are present in GpIIb/GpIIIa complex (CD41a) which is present on megakaryocytes (Mks) and platelets. CD41a is the earliest marker of megakaryocytopoiesis. The aim of this study was to analyse the morphology, phenotype, ploidy level and activity of FUT8 during induced differentiation/maturation of Mk progenitor cells in ex vivo culture. We used SU6656, a selective inhibitor of Src tyrosine kinases, as differentiation-inducing agent for Mks. The addition of SU6656 to the culture system of megakaryocytic progenitors from cord blood CD34+ cells and Meg-01 cell line induced their maturation towards later stages of Mk differentiation with increased activity of FUT8. We suggest FUT8 as a candidate for an early marker of differentiation and possibly of the ploidy level of Mks. We confirm a special status of FUT8 in megakaryocytopoiesis.
- Antoniewicz J, Bykowska K, Zdebska E, Kościelak J (1989) Human platelets release α-6-fucosyltransferase upon activation. FEBS Lett 244: 388-390.
- Aucoin JM, Koul O, Sajdel-Sulkowska EM, Baboval T, Smith FI (1998) The rat α1,3-fucosyltransferase (rFucT-IV) gene encodes both long and short forms of the enzyme which share the same intracellular location. Glycoconj J 15: 671-681.
- Bany-Laszewicz U, Kaminska J, Klimczak-Jajor E, Koscielak J (2004) The activity of α1,6-fucosyltransnferase during human megakaryocytic differentiation. Cell Mol Biol Lett 9: 145-152.
- Blake RA, Broome MA, Lui X, Wu J, Gishizky M, Sun L, Courtneidge SA (2000) SU6656, a selective Src family kinase inhibitor, used to probe growth factor signaling. Mol Cell Biol 20: 9018-9027.
- Cortes J, Rousselot P, Kim DW, Ritchie E, Hamerschlak N, Coutre S, Hochhaus A, Guilhot F et al. (2007) Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisis. Blood 109: 3207-3213.
- Druker BJ, Tamura S, Buchdunger E, Ohno S, Segal GM, Fanning S, Zimmermann J, Lydon NB (1996) Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med 2: 561-566.
- Guerriero R, Testa U, Gabbianelli M, Mattia G, Montesoro E, Mcioce G, Pace A, Ziegler B, Hassan HJ, Peschle C (1995) Unilineage megakaryocytic proliferation and differentiation of purified hematopoietic progenitors in serum-free liquid culture. Blood 86: 3725-3736.
- Ingley E (2008) Src family kinases: Regulation of their activities, levels and identification of new pathways. Biochim Biophys Acta 1784: 56-65.
- Jakubowska J, Stasiak M, Szulawska A, Bednarek A, Czyż M (2007) Combined effects of doxorubicin and STI571 on growth, differentiation and apoptosis of CML cell line K562. Acta Biochim Polon 54: 839-846.
- Kaminska J, Glick MC, Koscielak J (1998) Purification and characterisation of GDP-l-Fuc: N-acetyl β-d-glucosaminide α1-->6fucosyltransferase from human blood platelets. Glycoconj J 15: 783-788.
- Kaminska J, Dzieciol J, Koscielak J (1999) Triazine dyes as inhibitors and affinity ligands of glycosyltransferases. Glycoconj J 16: 719-723.
- Kaminska J, Musielak M, Nowicka A, Wozniewicz B, Koscielak J (2001) Neutrophils promote the release of α-6-fucosyltransferase from blood platelets through the action of cathepsin G and elastase. Biochimie 83: 739-742.
- Kaminska J, Klimczak-Jajor E, Bany-Laszewicz U, Skierski J, Zdebska E, Koscielak J (2007) Influence of Src kinases inhibitor, SU6656, on megakaryoblastic cell line Meg-01 (CML Ph+). Post Nauk Med 20: 304-308 (in Polish, with English summary).
- Koscielak J, Pacuszka T, Kubin J, Zdziechowska H (1987a) Serum α-6-fucosyltransferase is released from platelets during clotting of blood. Glycoconj J 4: 43-49.
- Koscielak J, Pacuszka T, Miller-Podraza H, Zdziechowska H (1987b) Activities of fucosyltransferases in sera of leukaemic patients: platelet origin of serum α-6-L-fucosyltransferase. Biochem Soc Trans 15: 603-606.
- Koscielak J, Antoniewicz-Papis J, Zdebska E, Maj S, Leszko B (1995) Activity of platelet α-6-fucosyltransferase is inversely related to blood platelet concentration. Acta Biochim Polon 42: 35-40.
- Lannutti BJ, Drachman JG (2004) Lyn tyrosine kinase regulates thrombopoietin-induced proliferation of hematopoietic cell lines and primary megakaryocytic progenitors. Blood 103: 3736-3743.
- Lannutti BJ, Shim MH, Blake N, Reems JA, Drachman JG (2003) Identification and activation of Src family kinases in primary megakaryocytes. Exp Hematol 31: 1268-1274.
- Lannutti BJ, Blake N, Reems JA, Gandhi MJ, Reems JA, Drachman JG (2005) Induction of polyploidization in leukemic cell lines and primary bone marrow by Src kinase inhibitor SU6656. Blood 105: 3875-3878.
- Li W, Nakagawa T, Koyama N, Wang X, Jin J, Mizuno-Horikawa Y, Gu J, Miyoshi E, Kato I, Honke K, Taniguchi N, Kondo A (2006) Down-regulation of trypsinogen expression is associated with growth retardation in α1,6-fucosyltransferase-deficient mice: attenuation of proteinase-activated receptor 2 activity. Glycobiology 16: 1007-1019.
- Long M (1998) Megakaryocyte differentiation events. Semin Hematol 35: 192-199.
- Majka M, Ratajczak MZ (2006) Biological role of the CXCR4-SDF-1 axis in normal human hematopoietic cells. Methods Mol Biol 332: 103-114.
- Miyazaki R, Ogata H, Iguchi T, Sogo S, Kushida T, Ito T, Inaba M, Ikehara S, Kabayashi Y (2000) Comparative analyses of megakaryocytes derived from cord blood and bone marrow. Br J Haematol 108: 602-609.
- Nixon B, Lu Q, Wassier MJ, Foote CI, Ensslin MA, Shur BD (2001) Galactosyltransferase function during mammalian fertilization. Cells Tissues Organs 168: 46-57.
- Ogura M, Morishima Y, Ohno R, Kato Y, Hirabayashi N, Nagura H, Saito H (1985) Establishment of a novel human megakaryoblastic leukemia cell line, MEG-01, with positive Philadelphia chromosome. Blood 66: 1384-1392.
- Raslova H, Kauffmann A, Sekkai D, Ripoche H, Larbret F, Robert T, Tronik Le Roux D, Kroemer G, Debili N, Dessen P, Lazar V, Vainchenker W (2007) Interrelation between polyploidization and megakaryocyte differentiation: a gene profiling approach. Blood 109: 3225-3234.
- Roskoski Jr R (2004) Src protein-tyrosine kinase structure and regulation. Biochem Biophys Res Commun 324: 1155-1164.
- Tsuji T, Osawa T (1986) Structures of the carbohydrate chains of membrane glycoproteins IIb and IIIa of human platelets. J Biochem 100: 1387-1389.
- Vainchenker W, Kieffer N (1988) Human megakaryocytopoiesis: In vitro regulation and characterization of megakaryocytic precursor cells by differentiation markers. Blood Rev 2: 102-107.
- van den Oudenrijn S, von Borne A, de Haas M (2000) Differences in megakaryocyte expansion potential between CD34+ stem cells derived from cord blood, peripheral blood, and bone marrow from adults and children. Exp Hematol 28: 1054-1061.
- Wilson MB, Schreiner SJ, Choi H-J, Kamens J, Smithgall TE (2002) Selective pyrrolo-pyrimidine inhibitors reveal a necessary role for Src family kinases in Bcr-Abl signal transduction and oncogenesis. Oncogene 21: 8075-8088.
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