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Titolo:
Activation of the Rap1 guanine nucleotide exchange gene, CalDAG-GEF I, in BXH-2 murine myeloid leukemia
Autore:
Dupuy, AJ; Morgan, K; von Lintig, FC; Shen, HF; Acar, H; Hasz, DE; Jenkins, NA; Copeland, NG; Boss, GR; Largaespada, DA;
Indirizzi:
Univ Minnesota, Ctr Canc, Inst Human Genet, Minneapolis, MN 55455 USA UnivMinnesota Minneapolis MN USA 55455 Genet, Minneapolis, MN 55455 USA Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA UnivMinnesota Minneapolis MN USA 55455 & Dev, Minneapolis, MN 55455 USA Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA Univ Calif San Diego La Jolla CA USA 92093 pt Med, La Jolla, CA 92093 USA NCI, Mouse Canc Genet Program, Frederick Canc Res & Dev Ctr, Frederick, MD21702 USA NCI Frederick MD USA 21702 ick Canc Res & Dev Ctr, Frederick, MD21702 USA
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 15, volume: 276, anno: 2001,
pagine: 11804 - 11811
SICI:
0021-9258(20010413)276:15<11804:AOTRGN>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
NEUROFIBROMATOSIS TYPE-1 GENE; R-RAS; CELLULAR-TRANSFORMATION; SIGNALING PATHWAY; INTEGRATION SITE; MEMBRANE-PROTEIN; NIH3T3 CELLS; MAP KINASE; PRODUCT; TC21;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
65
Recensione:
Indirizzi per estratti:
Indirizzo: Largaespada, DA Univ Minnesota, Ctr Canc, Inst Human Genet, Minneapolis, MN 55455 USA Univ Minnesota Minneapolis MN USA 55455 lis, MN 55455 USA
Citazione:
A.J. Dupuy et al., "Activation of the Rap1 guanine nucleotide exchange gene, CalDAG-GEF I, in BXH-2 murine myeloid leukemia", J BIOL CHEM, 276(15), 2001, pp. 11804-11811

Abstract

Here we report the recurrent proviral activation of the Rap1-specific guanine nucleotide exchange factor CalDAG-GEF I (Kawasaki, H., Springett, G. M., Toki, S., Canales, J. J., Harlan, P., Blumenstiel, J. P., Chen, E. J., Bany, I. A., Mochizuki, N., Ashbacher, A., Matsuda, M., Housman, D. E., and Graybiel, A. M. (1998) Proc. Natl. Acad. Sci. U.S.A. 95, 13288-13283; Correction (1999) Proc. Natl. Acad Sci. U.S.A. 96, 318) gene in BXH-2 acute myeloid leukemia. We also show that CalDAG-GEF I encodes two protein isoforms, afull-length isoform (CalDAG-GEF Ia) and a C-terminally truncated isoform (CalDAG-GEF Ib). Expression of the full-length CalDAG-GEF la isoform in Rat2fibroblasts enhances growth in low serum, whereas expression in Swiss 3T3 cells causes morphological transformation and increased saturation density. In FDCP1 myeloid cells, CalDAG-GEF Pa expression increases growth and saturation density in the presence of the diacylglycerol analogs phorbol 12-myristate 13-acetate (PMA), which activates CalDAG-GEF Pa exchange activity. Likewise, in 32DcI3 myeloblast cells, CalDAG-GEF Ia expression increases cell adherence to fibronectin in response to PMA and calcium ionophore and allows higher saturation densities and prolonged growth on fibronectin-coated plates. These effects were correlated with increased Rap1, but not Ras, protein activation following PMA. and calcium ionophore treatment. Our resultssuggest that Rap1-GTP delivers signals that favor progression through the cell cycle and morphological transformation, The identification of CalDAG-GEF I as a proto-oncogene in BXH-2 acute myeloid leukemia is the first evidence implicating Rap1 signaling in myeloid leukemia.

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Documento generato il 21/09/20 alle ore 12:28:28