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Evidence that the phl gene encodes a 160,000-dalton phosphoprotein with associated kinase activity.

机译:phl基因编码具有相关激酶活性的160,000道尔顿磷蛋白的证据。

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In chronic myelocytic leukemia, the human c-abl oncogene is translocated from chromosome 9 to a region on chromosome 22 designated as the breakpoint cluster region (bcr) (A. de Klein, A. Guerts van Kessel, G. Grosveld, C. R. Bartram, A. Hagemeyer, D. Bootsma, N. K. Spurr, N. Heisterkamp, J. Groffen, and J. R. Stephenson, Nature (London) 300:765-767, 1982; J. Groffen, J. R. Stephenson, N. Heisterkamp, A. de Klein, C. R. Bartram, and G. Grosveld, Cell 36:93-99.) Abnormal c-abl homologous mRNA and protein have been detected in the leukemic cells of patients with chronic myelocytic leukemia (E. Canaani, D. Stein-Saltz, E. Aghai, R. P. Gale, A. Berrebi, and E. Januszewicz, Lancet 1:593-595, 1984; S. J. Collins and M. T. Groudine, Proc. Natl. Acad. Sci. USA 80:4813-4817, 1983; R. P. Gale and E. Canaani, Proc. Natl. Acad. Sci. USA 81:5648-5652, 1984; J. B. Konopka, S. M. Watanabe, J. W. Singer, S. J. Collins, and O. N. Witte, Proc. Natl. Acad. Sci. USA 82:1810-1814, 1985). The abnormal mRNA represents a chimeric transcript consisting of 5' bcr and 3' c-abl sequences (G. Grosveld, J. Verwoerd, T. van Agthoven, A. de Klein, K. L. Ramachandran, N. Heisterkamp, K. Stam, and J. Groffen, Mol. Cell. Biol. 6:607-616, 1986; E. Shtivelman, B. Lifshitz, R. B. Gale, and E. Canaani, Nature (London) 315:550-554, 1985; K. Stam, N. Heisterkamp, G. Grosveld, A. de Klein, R. S. Verma, M. Coleman, H. Dosik, and J. Groffen, N. Engl. J. Med. 313:1429-1433, 1985). In the present study, we demonstrated that the abnormal c-abl protein is a fusion protein. In addition, the normal gene encompassing bcr sequences was shown to encode a 160,000-dalton phosphoprotein with an associated serine or threonine kinase activity. We propose that this gene be designated phl, reserving the term bcr for the region within the phl gene encompassing the Ph' translocation breakpoints.
机译:在慢性粒细胞白血病中,人类c-abl癌基因从9号染色体转移到22号染色体上的一个断点簇区域(bcr)(A。de Klein,A。Guerts van Kessel,G。Grosveld,CR Bartram, A.Hagemeyer,D.Bootsma,NK Spurr,N.Heisterkamp,J.Groffen和JR Stephenson,Nature(London)300:765-767,1982年; J.Groffen,JR Stephenson,N.Heisterkamp,A.de Klein ,CR Bartram和G. Grosveld,细胞36:93-99。)在慢性粒细胞性白血病患者的白血病细胞中已检测到异常的c-abl同源mRNA和蛋白质(E. Canaani,D。Stein-Saltz,E :Aghai,RP Gale,A。Berrebi和E. Januszewicz,柳叶刀1:593-595,1984; SJ Collins和MT Groudine,美国国家科学院院刊80:4813-4817,1983; RP Gale和E.Canaani,美国国家科学院学报81:5648-5652,1984; JB Konopka,SM Watanabe,JW Singer,SJ Collins和ON Witte,美国国家科学院学报82:1810- 1814,1985)。异常的mRNA代表由5'bcr和3'c-abl序列组成的嵌合转录物(G. Grosveld,J.Verwoerd,T.van Agthoven,A.de Klein,KL Ramachandran,N.Heisterkamp,K.Stam和J.Groffen,Mol.Cell.Biol.6:607-616,1986; E.Shtivelman,B.Lifshitz,RB Gale和E.Canaani,Nature(London)315:550-554,1985; K.Stam, N.Heisterkamp,G.Grosveld,A.de Klein,RS Verma,M.Coleman,H.Dosik和J.Groffen,N.Engl.J.Med.313:1429-1433,1985)。在本研究中,我们证明了异常的c-abl蛋白是融合蛋白。此外,显示出包含bcr序列的正常基因编码具有相关丝氨酸或苏氨酸激酶活性的160,000道尔顿磷蛋白。我们建议将该基因命名为phl,保留phl基因中包含Ph'易位转折点的区域的术语bcr。

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