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Fv2 encodes a truncated form of the Stk receptor tyrosine kinase

NATURE GENETICS 1999年第2期23卷 159-165页

作者： Persons, DA Paulson, RF Loyd, MR Herley, MT Bodner, SM Bernstein, A Correll, PH Ney, PA St Jude Childrens Res Hosp Dept Biochem Memphis TN 38105 USA St Jude Childrens Res Hosp Dept Expt Hematol Memphis TN 38105 USA St Jude Childrens Res Hosp Dept Pathol Memphis TN 38105 USA Penn State Univ Dept Vet Sci University Pk PA 16802 USA Univ Toronto Mt Sinai Hosp Samuel Lunenfeld Res Inst Program Mol Biol & Canc Toronto ON M5G 1X5 Canada Univ Toronto Mt Sinai Hosp Dept Mol & Med Genet Toronto ON M5G 1X5 Canada

The Friend virus susceptibility 2 (Fv2) locus encodes a dominant host factor that confers susceptibility to Friend virus-induced erythroleukaemia in mice. We mapped Fv2 to a 1.0-Mb interval that also contained the gene (Ron) encoding the stem cell kinase receptor (Stk). A truncated form of Stk (Sf-stk), which was the most abundant form of Stk in Fv2-sensitive (Fv2(ss)) erythroid cells, was not expressed in Fv2 resistant (Fv2(rr)) cells. Enforced expression of Sf-stk conferred susceptibility to Friend disease, whereas targeted disruption of Ron caused resistance. We conclude that the Fv2 locus encodes Ron, and that a naturally expressed, truncated form of Stk confers susceptibility to Friend virus-induced erythroleukaemia.

关键词： 3T3细胞碱基序列染色体图克隆分子物理图谱弗林德鼠白血病病毒基因表达疾病遗传易感性白血病幼红细胞急性/遗传学小鼠近交AKR 小鼠近交BALBC 小鼠近交C3H 小鼠近交CBA 小鼠近交NZB 小鼠近交系分子序列数据鼠科蛋白质亚型/遗传学受体蛋白质酪氨酸激酶类/遗传学受体细胞表面/遗传学逆转录病毒科感染/遗传学种特异性脾/代谢脾/病理学肿瘤病毒感染/遗传学动物小鼠

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Inositides in the nucleus:: Further developments on phospholipase Cβ₁ signalling during erythroid differentiation and IGF-I induced mitogenesis

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ADVANCES IN ENZYME REGULATION, VOL 39 1999年第1期39卷 287-297页

作者： Cocco, L Capitani, S Barnabei, O Gilmour, RS Rhee, SG Manzoli, FA Univ Bologna Inst Anat I-40126 Bologna Italy Univ Ferrara Inst Anat I-44100 Ferrara Italy Univ Bologna Dept Biol I-40126 Bologna Italy NHLBI Lab Cell Signalling NIH Bethesda MD 20892 USA Univ Auckland Sch Med Auckland New Zealand

Inositol lipids originally shown to be metabolized in the cytosol have been detected also in the nucleus, where they are both synthesized and hydrolyzed. In the case of erythroid differentiation of murine erythroleukemia cells (Friend cells) it has been previously shown that PLC beta 1, which is the major nuclear PLC, undergoes down-regulation upon treatment with DMSO or tiazofurin which act as differentiative agents. On the contrary, i.e., during IGF-I induced mitogenesis, it has been shown that PLC beta 1 is rapidly activated and this event is essential for the onset of DNA synthesis. Even though its key role in cell growth has been shown, both the mechanism by which nuclear PLC beta 1 is activated and the direct relationship with erythroid differentiation are still unknown. We have addressed the question if PLC beta 1 expression and activity in the nucleus are directly related or not to the establishment of the differentiated state and we have checked the two main ways of activation, i.e., via G-protein or via phosphorylation, in order to establish whether nuclear PLC beta 1 is regulated the same way as the one at the plasma membrane or not. The data reported here show that nuclear PLC beta 1 is responsible for a continuous recycling of Friend cells, acting as a negative regulator of differentiation and that its activation is dependent on the phosphorylation state.

关键词： 3T3细胞细胞分裂/药物作用细胞核/代谢红细胞生成/药物作用红细胞生成/生理学弗林德鼠白血病病毒胰岛素样生长因子Ⅰ/药理学同工酶类/遗传学同工酶类/代谢白血病幼红细胞急性/代谢白血病幼红细胞急性/病理学有丝分裂原/药理学磷脂酰肌醇类/代谢 RNA 反义/遗传学信号传导转染肿瘤细胞培养的动物小鼠

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CONSTITUTIVE SYNTHESIS OF GLOBINS WITHIN MOST OF THE MEMBERS OF AN UNINDUCED, PROLIFERATING POPULATION OF FRIEND-ERYTHROLEUKEMIC CELLS

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DEVELOPMENTAL BIOLOGY 1979年第2期69卷 576-588页

作者： REEVES, R CSERJESI, P Department of Zoology University of British Columbia Vancouver B. C. Canada V6T 1W5

The proteins synthesized by Friend [mouse] erythroleukemic cells (clone 745), before and after they are induced by treatment with dimethylsulfoxide to undergo overt erythroid maturation, were analyzed by a number of biochemical methods. None of these techniques revealed any consistent observable differences (other than quantitative variations in the concentrations of particular proteins) between the uninduced and the induced cells. Various classes of cellular proteins (whole cell, cytoplasmic and nuclear) appear to be very similar in the 2 types of cells when analyzed by 2-dimensional gel electrophoresis. The strain-specific Hb of DBA/2 mice (the line from which the Friend cells were derived by viral transformation) were synthesized in both the uninduced and the induced cells but at apparently markedly different rates. A monospecific antibody preparation against purified DBA/2 mouse .alpha.- and .beta.-globins was used to quantify the amount of these proteins in Friend cells during the course of dimethylsulfoxide-induced differentiation. Rocket gel immunoelectrophoresis, radial immunodiffusion analysis and competitive radioimmunoassay revealed that the uninduced Friend cells contained, on the average, about 0.45 pg of Hb/cell and this amount increased about 32-fold (to about 14.4 pg/cell) after 5 days of induction. The antibody preparation in indirect immunofluorescence studies revealed the constitutive synthesis of low levels of globins in virtually all of the uninduced, actively dividing, leukemia cells. The standardly used benzidine staining method for detecting Hb apparently is insensitive for the detection of low levels of these proteins. The cells in this particular leukemic population are already differentiated. The cells may represent an intermediate stage of erythroid maturation whose further progress along the normal in vivo terminal differentiation pathway is blocked by viral transformation. Perhaps various inducers, such as dimethylsulfoxide, may enable

关键词：联苯胺类细胞分裂细胞系细胞转化病毒克隆细胞/代谢二甲亚砜/药理学荧光抗体技术弗林德鼠白血病病毒珠蛋白类/生物合成血红蛋白类/分析免疫扩散白血病幼红细胞急性/代谢白血病实验性/代谢动物小鼠

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TOXOPLASMOSIS TRANSMISSION BY BLOOD-TRANSFUSION

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DEUTSCHE MEDIZINISCHE WOCHENSCHRIFT 1978年第41期103卷 1598-1602页

作者： WERK, R BOMMER, W Hygiene-Institut Lehrstuhl für Allgemeine Hygiene Universität Göttingen

T-cells of the chicken tumour HPRS-1, mouse mastocytoma cells, Friend virus-transformed erythroleukaemia cells as well as normal human, mouse and chick erythrocytes were tested for their receptivity to toxoplasma infection. The studies indicate that T-cells and mastocytoma cells, which may be counted as part of the white blood cell series, have the highest invasion rate after incubation with toxoplasma. Friend-erythroleukaemia cells were less often affected; mature human, mouse and chick erythrocytes were refractory. The results suggest that cells of the white blood cell series are receptive to toxoplasma infection but that nucleated precursors of the red series may also be so, while mature erythrocytes cannot be infected. The possibility of transmission of toxoplasmosis by blood transfusion can no longer be doubted.

关键词：鸡红细胞/病理学弗林德鼠白血病病毒白血病幼红细胞急性/病理学肥大细胞肉瘤/病理学肿瘤实验性/病理学 T淋巴细胞/病理学弓形虫病/传播动物人类小鼠

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MECHANISM OF GENETIC RESISTANCE TO IMMUNE SUPPRESSION BY FRIEND LEUKEMIA-VIRUS - ROLE OF MARROW-DEPENDENT CELLS

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ANNALS OF THE NEW YORK ACADEMY OF SCIENCES 1976年第SEP3期276卷 217-228页

作者： KUMAR, V ECKNER, RJ BENNETT, M BOSTON UNIV SCH MEDDEPT PATHOLBOSTONMA 02118

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REVERSAL OF IMMUNOSUPPRESSION INDUCED BY MURINE LEUKEMIA VIRUSES

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ANNALS OF THE NEW YORK ACADEMY OF SCIENCES 1976年第SEP3期276卷 431-441页

作者： BENDINELLI, M TONIOLO, A FRIEDMAN, H UNIV PISA INST MICROBIOLI-56100 PISAITALY ALBERT EINSTEIN MED CTR DEPT MICROBIOLPHILADELPHIAPA 19141

BALB/c mice infected with Rowson-Parr virus, a lymphatic leukemia virus isolated from the Friend complex, undergo a rapid depression of antibody response. Spleen cells from these mice in culture show a similar deficit in the response to stimulation with sheep red cells and inhibit the reactivity of normal splenocytes. In an attempt to reverse this immunosuppression, near normal responses were obtained in vitro from infected splenocytes by increasing antigen dose, by adding E. coli lipopolysaccharide, or, more effectively, by cocultivating with small numbers of unfractionated or T cell-depleted peritoneal exudate cells (PC), whereas other manipulations proved ineffective. PC did not prevent the inhibition of normal splenocytes by infected spleen cells, but exhibited substantial restorative activity in vivo. In similar experiments, the immunosuppression exerted by the entire Friend complex could be reversed by PC in vitro but not in vivo. These results indicate that a functional deficit of macrophages may be partially responsible for the immunological impairment induced by leukemia viruses and suggest rational approaches to evaluate the relevance of this impairment to oncogenesis.

关键词：抗体生成/药物作用抗原腹水液/免疫学剂量效应关系免疫红细胞/免疫学弗林德鼠白血病病毒免疫球蛋白M/生物合成免疫抑制法白血病实验性/免疫学脂多糖类/药理学巨噬细胞/免疫学小鼠近交BALBC 脾/免疫学肿瘤病毒感染/免疫学动物小鼠

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AFFERENT AND EFFERENT INTERFERENCE OF CELL-MEDIATED CYTOTOXIC REACTIONS BY HEPARIN

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JOURNAL OF THE NATIONAL CANCER INSTITUTE 1976年第2期57卷 455-457页

作者： TING, CC NCI CELL BIOL LABBETHESDAMD 20014

Heparin influenced the induction (afferent interference) and effector (efferent interference) phases of cell-mediated cytotoxic reactions against FBL-3 cells, a syngeneic Friend virus-induced leukemia in inbred C57BL/6 mice. Heparin was cytotoxic at high concentrations (greater than or equal to 100 U/ml) and inhibitory for cell-mediated cytotoxic response at lower concentrations (less than or equal to 50 U/ml).

关键词：细胞毒性试验免疫弗林德鼠白血病病毒肝素/药理学免疫细胞/药物作用白血病实验性/免疫学小鼠近交C57BL 动物小鼠

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INVIVO DISTINCTION BETWEEN A TARGET-CELL FOR FRIEND VIRUS (FV-P) AND MURINE HEMATOPOIETIC STEM-CELLS

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JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE 1976年第2期57卷 443-445页

作者： NASRALLAH, AG MCGARRY, MP SUNY BUFFALO ROSWELL PK DIV DEPT PHYSIOL BUFFALO NY 14263 USA NEW YORK STATE DEPT HLTH ROSWELL PK MEM INST DEPT BIOL RESOURCES BUFFALO NY 14263 USA

Busulfan (BU) treatment of DBA/2 mice with hypertransfusion (HT)-induced polycythemia resulted in an ablation of detectable hematopoietic stem cells (CFUS) in pooled marrow from the long bones. Daily injections of erythropoietin (EP) stimulated an EP-responsive population of cells in the absence of detectable CFUS. Mice treated with BU and EP and having HT-induced polycythemia were inoculated with the polycythemia inducing strain of Friend virus (FVP) and determinations were made for the presence of tumor colony-forming units (tCFU). No change in CFUS/106 bone marrow cells was detected as a result of EP treatment. tCFU were increased more than 100 fold in HT-BU-EP-treated mice compared with saline-treated controls. The demonstration of tCFU in mice in which CFUS were not detectable indicated that this leukemogenic effect of FVP could occur in the absence of the pluripotent stem cell. The increased numbers of this FVP target cell in EP-stimulated, BU-treated mice with HT-induced polycythemia supported the model locating the target for this effect in the EP-responsive cell population.

关键词：白消安/药理学细胞转化肿瘤红细胞/微生物学红细胞生成素/药理学弗林德鼠白血病病毒造血干细胞/药物作用造血干细胞/微生物学小鼠近交DBA 红细胞增多症/病理学动物女(雌)性小鼠

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DISCUSSION PAPER - PROTECTIVE IMMUNITY IN LEUKEMIC MICE TREATED WITH SPECIFIC IMMUNOGENIC RNA

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ANNALS OF THE NEW YORK ACADEMY OF SCIENCES 1976年第SEP20期277卷 708-715页

作者： FRIEDMAN, H ALBERT EINSTEIN MED CTR DEPT MICROBIOL PHILADELPHIA PA 19141 USA

Mice were actively immunized against Friend leukemia virus tumorigenesis by vaccination with cell-free homogenates derived from infected splenocytes emulsified in Freund's adjuvant. Adoptive immunity was also achieved by transferring splenocytes from actively immunized donor animals intravenously into syngeneic recipient animals challenged with the virus. Furthermore, RNA-rich extracts derived from spleens of actively immunized donor animals were capable of transferring immunity to FLV leukemia when injected into recipient animals challenged with the virus. The "immune RNA," when incubated with normal splenocytes in vitro, followed by washing, resulted in a cell population that also induced adoptive immunity after transfer to normal animals challenged with virus either before, simultaneously with, or after injection of the treated splenocytes. RNase, but not DNase or other enzymes, inactivated the biologie activity of the protective RNA from immune donors. In addition, isogeneic mouse serum that contained neutralizing antibody to FLV also inhibited the protective effect of the specific RNA; sera from control mice immunized with unrelated antigens failed to neutralize the specific RNA. These results indicate that an RNA extract that contains a virus-associated or -induced antigen is formed in the spleens of actively immunized animals and possesses the ability to either directly induce protective immunity in recipient animals challenged with virus or, indirectly, to convert normal splenocytes in vitro to adoptively confer immunity to similar recipients. Further investigations concerning the mechanism by which such immunogenic RNA functions in vivo and in vitro, as well as the physicochemical nature of the RNA complex, especially that portion associated with the tumor virus-associated antigen, are needed.

关键词：抗原肿瘤弗林德鼠白血病病毒免疫法被动白血病实验性/免疫学白血病实验性/微生物学白血病实验性/治疗小鼠近交BALBC RNA/免疫学 RNA/治疗应用脾/免疫学脾/病理学脾大/病因学脾大/微生物学动物男(雄)性小鼠

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BUDR INHIBITION OF POST-DMSO-INDUCED ERYTHROLEUKEMIA CELL-DIFFERENTIATION INVITRO

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BRITISH JOURNAL OF CANCER 1976年第5期33卷 561-563页

作者： PREISLER, HD ROSWELL PK MEM INST DEPT MED A BUFFALO NY 14263 USA

The addition of BUdR [bromodeoxyuridine] to secondary cultures of control or DMSO [dimethylsulfoxide] treated mouse Friend leukemia cells had no effect on cell growth during the 3 day secondary culture period. The amount of heme synthesized per cell and the proportion of benzidine positive cells was decreased in each instance by .apprx. 50%. It seems surprising that the increment in the amount of heme/106 cells during secondary culture appeared to be less than the increment in heme per culture. This observation arises because the rate of increase in differentiated cells during secondary culture was less than the rate of increase in undifferentiated cells in the same culture. The proportion of differentiated cells in the secondary culture actually declined. These leukemic cells continue to synthesize and accumulate globin mRNA after removal of DMSO from the culture medium, and interference with this process inhibits differentiation during secondary culture in DMSO free medium.

关键词：溴脱氧尿苷/药理学细胞分化/药物作用细胞培养的二甲亚砜/药理学弗林德鼠白血病病毒白血病幼红细胞急性/化学诱导白血病幼红细胞急性/病理学白血病实验性/病理学动物

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