Ectopic Expression of Mer on Jurkat Cells and Its Anti-Apoptosis Effect.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4098-4098
Author(s):  
Lei Fan ◽  
Liqian Xie ◽  
Fei Shen ◽  
Lan Dai ◽  
Jianyong Li ◽  
...  
Keyword(s):  
T Cells ◽  
Tyrosine Kinase ◽  
Caspase 3 ◽  
Ectopic Expression ◽  
Leukemia Cell ◽  
Annexin V ◽  
Jurkat Cells ◽  
Leukemia Cell Line ◽  
Serum Starvation ◽  
Significant Difference

Abstract BACKGROUND & OBJECTIVE: Mer is one member of Axl receptor tyrosine kinase family; its ligand Gas6 can bind Mer, then stimulate the tyrosine kinase activity and downstream cell signal pathway of Mer, and take part in cell inflammation, apoptosis and thrombosis. There are more and more reports on Mer function, while few on its association with malignant diseases. This study was to detect the expression of Mer on T-cell leukemia cell line--Jurkat, and investigate its anti-apoptosis function and the mechanism. METHODS: Flow cytometry (FCM) was used to detect Mer expression on normal T cells and Jurkat cells. RNA interference (RNAi) was used to block the expression of Mer on Jurkat cells. The effect of Mer on the proliferation of Jurkat cells was assessed by MTT assay, and its effect on serum starvation-induced apoptosis was evaluated by FCM with Annexin V/PI double staining. The expression of apoptosis-associated genes Bcl-2 and Caspase-3 in Jurkat cells was detected by real-time polymerase chain reaction (PCR) after Mer blocking. RUSELTS: Mer was not expressed in normal T cells both in peripheral blood and bone marrow, but highly expressed in Jurkat cells with a positive rate of 51.1%±5.2%. The inhibition rate of Mer expression in Jurkat cells by RNAi was 86.0%±10.3%. After 48-hour serum starvation, the apoptosis rate was 15.3%±4.3% in Mer-blocking Jurkat cells, and only 1.5%±1.0% in control Jurkat cells(P<0.01). There was no significant difference in Jurkat cell proliferation rate between these 2 groups. After Mer blocking, Bcl-2 expression was decreased by 42.7%±8.6% of control(P<0.01), Caspase-3 expression showed no significant change. CONCLUSION: Mer is highly expressed in Jurkat cells, and could inhibit cell apoptosis via Bcl-2 signaling pathway.

Quercetin Promotes Cell Cycle Arrest and Apoptosis and Attenuates the Proliferation of Human Chronic Myeloid Leukemia Cell Line-K562 Through Interaction with HSPs (70 and 90), MAT2A and FOXM1

2019 ◽  
Vol 19 (12) ◽  
pp. 1523-1534 ◽  
Author(s):  
Ali Hassanzadeh ◽  
Elham Hosseinzadeh ◽  
Saleheh Rezapour ◽  
Ghasem Vahedi ◽  
Navideh Haghnavaz ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Kinase Inhibitors ◽  
Philadelphia Chromosome ◽  
Leukemia Cell ◽  
Annexin V ◽  
Leukemic Cells ◽  
Leukemia Cell Line ◽  
Genes Expression ◽  
K 562 Cells ◽  
Induced Apoptosis

Background: Chronic Myeloid Leukaemia (CML) starts in certain blood-forming cells of the bone marrow when cells acquire Philadelphia chromosome. Nowadays, scientists attempt to find novel and safe therapeutic agents and approaches for CML therapy using Tyrosine Kinase Inhibitors (TKIs), CML conventional treatment agents, has some restrictions and also adverse effects. Recently, it has been proposed that phytochemicals, such as flavonoids due to their low side effects and notable safety have the potential to be used for CML therapy. Materials and Methods: K-562 cells were exposed with three concentrations of the querectin (10, 40 and 80µM) for 12, 24 and 48 hours. After that, these cells apoptosis rate was estimated using Annexin-V/PI staining and flowcytometry analysis, and their proliferation rate was evaluated using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT). Finally, the expression of the 70 and 90 kilodalton heat shock proteins (HSP70 and 90), methionine adenosyltransferase 2A (MAT2A), Forkhead box protein M1 (FOXM1), caspase-3 and -8, Bcl-X(L) and Bax involved in leukemic cells survival and proliferation was assessed using Real-Time PCR within 12, 24 and 48 hours after exposure with quercetin 40 and 80µM. Results: Considering consequences, querecetin induced apoptosis in K-562 cells, and also abrogated these cells proliferation. On the other hand, RT-PCR results showed a reduction in some of the candidate genes expression, especially HSP70, Bcl-X(L) and FOXM1, when cells were treated with quercetin 40 and 80µM. Also, Bax, caspase-3 and caspase-8 expression was significantly improved in K-562 cells upon quercetin exposure. Conclusion: We concluded that CML therapy by querecetin due to its anti-proliferative and anti-survival potentials could lead to the promising therapeutic outcome through targeting major survival and proliferation involved genes expression.

scholarly journals 3ʹS,4ʹS-Disenecioylkhellactone from the Roots of Peucedanum Japonicum Induces Apoptosis in HL-60 Cells ​

2020 ◽  
Author(s):  
Kyung-Yun Kang ◽  
Sung-Ju Lee ◽  
Hyun-Ji Kim ◽  
Heonjoong Kang ◽  
Sang-Jip Nam ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Caspase 3 ◽  
Biological Activities ◽  
Leukemia Cell ◽  
Annexin V ◽  
The Philippines ◽  
Cell Counting ◽  
Leukemia Cell Line ◽  
Resonance Spectroscopy ◽  
Human Leukemia

Abstract Background: The root of Peucedanum japonicum is used in traditional medicine in Japan, the Philippines, China, and Korea, and it has been reported to have a variety of biological activities, including anticancer activity. Inducing apoptosis in tumor cells has become a major focus of antitumor drug development; therefore, we studied the apoptotic effects of the MeOH/CH2Cl2 extract of the roots of P. japonicum and its components on HL-60 cells (a human leukemia cell line).Methods: Compounds were purified using solvents with varying polarities followed by column chromatography (reverse phase), and the structures were confirmed using nuclear magnetic resonance spectroscopy. The viabilities of HL-60, A549, and MCF-7 cells were determined using the cell counting kit-8 (CCK-8) assay. Analysis of apoptosis signaling was performed only with HL-60 cells, and cell cycle progression, Annexin V/propidium iodide (PI) staining (analyzed by flow cytometry), the mitochondrial membrane potential (MMP, as analyzed by flow cytometry), and caspase-3, 8, and 9 activity (determined using the caspase-3, -8, and -9 activity kit according to the manufacturer’s protocol) were evaluated.Results: Two coumarin molecules, (-)-isosamidin (1) and 3ʹS,4ʹS disenecioylkhellactone (2), were isolated by bioactivity-guided fractionation. Only compound 2 showed cytotoxicity in HL-60 cells, which occurred due to increases in the sub-G1 population and the initiation of early and late apoptosis as determined by Annexin V/PI staining. In addition, decreases in the MMP were observed in HL-60 cells treated with compound 2. Several apoptotic features were observed, including increased cleavage of caspase-3, -8, and -9. Moreover, treatment with Z-DEVD-FMK (a caspase-3 inhibitor), Z-IETD-FMK (a caspase-8 inhibitor), or Z-LEHD-FMK (a caspase-9 inhibitor) significantly inhibited cell cytotoxicity.Conclusions: We provide evidence that compound 2 induces apoptosis in HL-60 cells.

scholarly journals Deep sequencing reveals two Jurkat subpopulations with distinct miRNA profiles during camptothecin-induced apoptosis

2017 ◽  
Author(s):  
İpek Erdoğan ◽  
Mehmet İlyas Coşacak ◽  
Ayten Nalbant Aldanmaz ◽  
Bünyamin Akgül
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Cell Lines ◽  
Deep Sequencing ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Leukemia Cell ◽  
Jurkat Cells ◽  
Cellular Heterogeneity ◽  
Leukemia Cell Line

AbstractmicroRNAs (miRNAs) are small non-coding RNAs of about 19-25 nt that regulate gene expression post-transcriptionally under various cellular conditions, including apoptosis. The miRNAs involved in modulation of apoptotic events in T cells are partially known. However, heterogeneity associated with cell lines makes it difficult to interpret gene expression signatures especially in cancer-related cell lines. Treatment of Jurkat T cell leukemia cell line with the universal apoptotic drug, camptothecin, resulted in identification of two Jurkat sub-populations: one that is sensitive to camptothecin and the other being rather intrinsically resistant. We sorted apoptotic Jurkat cells from the non-apoptotic ones prior to profiling miRNAs through deep sequencing. Our data showed that a total of 184 miRNAs were dysregulated. Interestingly, apoptotic and non-apoptotic sub-populations exhibited a distinct miRNA expression profile. In particular, 6 miRNAs were inversely expressed in these two sub-populations. The pyrosequencing results were validated by real time qPCR. Altogether these results suggest that miRNAs modulate apoptotic events in T cells and that cellular heterogeneity requires careful interpretation of miRNA expression profiles obtained from drug-treated cell lines.

Oridonin, An Ent-Kaurane Diterpenoid, Shows Antileukemic Effect and Enhances the Effect of Indarubicin on Human T-Cell Leukemia Cell Line

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4933-4933 ◽  
Author(s):  
Kangni Wu ◽  
Yanmin Zhao ◽  
Haowen Xiao ◽  
Lifei Zhang ◽  
Lizhen Liu ◽  
...  
Keyword(s):  
Low Dose ◽  
Caspase 3 ◽  
Leukemia Cell ◽  
Inhibitory Effect ◽  
Jurkat Cells ◽  
Leukemia Cell Line ◽  
Combination Effect ◽  
Hoechst 33258 ◽  
Human T Cell ◽  
Dose Dependent

Abstract Abstract 4933 Introduction Acute lymphoblastic leukemia (ALL) is the most common type of leukemia in young children, and also affects adults, especially those aged 65 years or older. Although the outcome of children with ALL has been improved dramatically with current chemotherapy strategy, adult patients still have a worse outcome and the incidence of relapse remains high either in children or adult patients. Furthermore, there has been very little progress in improving the outcome of patients who experience relapse. Oridonin, an ent-kaurane diterpenoid derived from the herbal Rabdosia rubescens, has been proved to have significant antitumor effect on a large variety of cancer cells. In this study, we aimed to assess whether oridonin had antileukemic effection and the possibility of combination effect with indarubicin (IDA), an important component commonly used in T-ALL induction regimen. Methods Human T-cell leukemia cell line Jurkat cells in culture medium were treated with different concentrations of oridonin (1umol/L~ 20umol/L) for 24h and 48h. Cell Counting Kit-8 (CCK8) assay was used to detect the cell growth inhibitory rate. Apoptosis was measured with flow cytometric (FCM) by staining cells with Annexin V-fluorescein-isothiocyanate(FITC) and propidium iodide (PI). Hoechst 33258 staining was used to observe the apoptotic morphology. The expression of caspase-3, caspase-8 and other apoptosis modulators, including Bcl-2 family members, was analyzed by western blotting. When the combination effect of oridonin and indarubicin was investigated, oridonin was given one hour before indarubicin. The calculation of combined effect was used Isobologram Analysis. Results CCK8 assay revealed that oridonin could significantly inhibit the growth of Jurkat cells in vitro. The suppression was both time- and dose-dependent. The concentration of oridonin lower than 5 umol/L showed little inhibitory effect, but it presented significant inhibition of the proliferation at a higher concentration, especially when the concentration was higher than 10 umol/L. The 50% inhibitory concentration (IC50) values for 24h and 48h were 9.44 and 9.06 umol/L respectively. After Jurkat cells were treated with higher than 5 umol/L of oridonin for 24–48h., the percentage of Annexin VFITC positive cells was gradually increased in a time and dose-dependent manner and the percentage of Annexin VFITC positive cells could reach 40% to 50% after 10 umol/L of oridonin treatment for 48h. Marked morphological changes of cell apoptosis including condensation of chromatin and nuclear fragmentation were observed using Hoechst 33258 stain after 48h. Western blotting analysis showed cleavage of the caspase-3 zymogen protein (32 kDa) with the appearance of its 20-kDa subunit when apoptosis occurred; Expression of Bcl-2 was downregulated significantly after the cells were treated with oridonin for 24 h. The expression of caspase-8 remained constant before and after apoptosis occurred. We therefore concluded that oridonin has significant antiproliferation effects on Jurkat cells by activation of caspase-3 as well as down-regulation of anti-apoptotic protein Bcl-2. The 24h IC50 of IDA for Jurkat cells was 25.85nmol/L. When combined with 1umol/L of oridonin, the IC50 of IDA decreased to 4.93nmol/L. The combine index was < 1, indicating the synergistic antitumor effect of IDA and oridonin. The data from FCM showed that 2.5 umol/L of oridonin could augment the apoptosis effect of 2.5nmol/L of IDA from 5.1% to 12.7%. During the experiment, we found that oridonin given one hour before IDA could make a better combination effect than given simultaneously. We also discovered that low dose oridonin (lower than 5 umol/L) had little inhibitory effect on normal bone marrow mononuclear cells. Conclusions The results showed oridonin could effectively induce ALL cells apoptosis, and in low dose showed a significant synergistic effect with IDA, indicating oridonin may serve as a potential and secure antileukemia reagent for ALL, especially in the combination chemotherapy. The underlying machanisms of the combination effect with anthracycline should be explored. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Non-Viral Transfection of Human T Lymphocytes

Processes ◽  
2018 ◽  
Vol 6 (10) ◽  
pp. 188 ◽  
Author(s):  
Simon Riedl ◽  
Patrick Kaiser ◽  
Alexander Raup ◽  
Christopher Synatschke ◽  
Valérie Jérôme ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Mammalian Cells ◽  
Large Scale ◽  
Leukemia Cell ◽  
Jurkat Cells ◽  
Leukemia Cell Line ◽  
Human T Lymphocytes ◽  
Human T Cell ◽  
Viral Transfection

The genetic modification of human T lymphocytes with established non-viral methods is inefficient. Linear polyethylenimine (l-PEI), one of the most popular non-viral transfection agents for mammalian cells in general, only achieves transfection rates in the single digit percentage range for these cells. Here, a well-defined 24-armed poly(2-dimethylamino) ethyl methacrylate (PDMAEMA) nanostar (number average of the molecular weight: 755 kDa, polydispersity: <1.21) synthesized via atom transfer radical polymerization (ATRP) from a silsesquioxane initiator core is proposed as alternative. The agent is used to prepare polyplexes with plasmid DNA (pDNA). Under optimal conditions these polyplexes reproducibly transfect >80% of the cells from a human T-cell leukemia cell line (Jurkat cells) at viabilities close to 90%. The agent also promotes pDNA uptake when simply added to a mixture of cells and pDNA. This constitutes a particular promising approach for efficient transient transfection at large scale. Finally, preliminary experiments were carried out with primary T cells from two different donors. Results were again significantly better than for l-PEI, although further research into the response of individual T cells to the transfection agent will be necessary, before either method can be used to routinely transfect primary T lymphocytes.

scholarly journals Antiapoptotic Activity of the Herpesvirus Saimiri-Encoded Bcl-2 Homolog: Stabilization of Mitochondria and Inhibition of Caspase-3-Like Activity

1998 ◽  
Vol 72 (7) ◽  
pp. 5897-5904 ◽  
Author(s):  
Tobias Derfuss ◽  
Helmut Fickenscher ◽  
Michael S. Kraft ◽  
Golo Henning ◽  
Doris Lengenfelder ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Leukemia Cell ◽  
Death Receptor ◽  
Mitochondrial Damage ◽  
Jurkat Cells ◽  
Leukemia Cell Line ◽  
Herpesvirus Saimiri ◽  
Human Leukemia ◽  
Host Cell Apoptosis ◽  
Human Leukemia Cell Line

ABSTRACT Viruses have evolved different strategies to interfere with host cell apoptosis. Herpesvirus saimiri (HVS) and other lymphotropic herpesviruses code for proteins that are homologous to the cellular antiapoptotic Bcl-2. In this study HVS-Bcl-2 was stably expressed in the human leukemia cell line Jurkat and in the murine T-cell hybridoma DO to assess its antiapoptotic spectrum and to gain further insight into its mode of action. HVS- Bcl-2 prevented apoptosis that occurs as a result of a disturbance of intracellular homeostasis by, for example, DNA damage or menadione, which gives rise to oxygen radicals. In Jurkat cells, HVS-Bcl-2 also inhibited apoptosis mediated by the death receptor CD95. In DO cells, HVS-Bcl-2 did not interfere with CD95-mediated apoptosis but blocked dexamethasone-induced cell death. Mitochondrial damage is a central coordinating event in apoptosis induced by different stimuli. To assess the integrity of mitochondria, we used rhodamine 123, which is released upon disturbance of the mitochondrial membrane potential, and determined the release of cytochrome c into the cytosol. Both signs of mitochondrial damage were prevented by HVS-Bcl-2. This viral protein also inhibited the generation of caspase-3-like DEVDase activity and blocked the cleavage of poly(ADP-ribose) polymerase, a natural substrate of caspase-3-like proteases. In conclusion, HVS-Bcl-2 protects against a great variety of apoptotic stimuli, stabilizes mitochondria, and acts upstream of the generation of caspase-3-like activity.

Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor

Blood ◽  
2000 ◽  
Vol 96 (3) ◽  
pp. 925-932 ◽  
Author(s):  
Michael C. Heinrich ◽  
Diana J. Griffith ◽  
Brian J. Druker ◽  
Cecily L. Wait ◽  
Kristen A. Ott ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Map Kinase ◽  
Cell Line ◽  
Cellular Proliferation ◽  
Kinase Activity ◽  
Leukemia Cell ◽  
Myelogenous Leukemia ◽  
Leukemia Cell Line ◽  
Tyrosine Kinase Activity ◽  
Sti 571

Abstract STI 571 (formerly known as CGP 57148B) is a known inhibitor of the c-abl, bcr-abl, and platelet-derived growth-factor receptor (PDGFR) tyrosine kinases. This compound is being evaluated in clinical trials for the treatment of chronic myelogenous leukemia. We sought to extend the activity profile of STI 571 by testing its ability to inhibit the tyrosine kinase activity of c-kit, a receptor structurally similar to PDGFR. We treated a c-kit expressing a human myeloid leukemia cell line, M-07e, with STI 571 before stimulation with Steel factor (SLF). STI 571 inhibited c-kit autophosphorylation, activation of mitogen-activated protein (MAP) kinase, and activation of Akt without altering total protein levels of c-kit, MAP kinase, or Akt. The concentration that produced 50% inhibition for these effects was approximately 100 nmol/L. STI 571 also significantly decreased SLF-dependent growth of M-07e cells in a dose-dependent manner and blocked the antiapoptotic activity of SLF. In contrast, the compound had no effect on MAP kinase activation or cellular proliferation in response to granulocyte-macrophage colony-stimulating factor. We also tested the activity of STI 571 in a human mast cell leukemia cell line (HMC-1), which has an activated mutant form of c-kit. STI 571 had a more potent inhibitory effect on the kinase activity of this mutant receptor than it did on ligand-dependent activation of the wild-type receptor. These findings show that STI 571 selectively inhibits c-kit tyrosine kinase activity and downstream activation of target proteins involved in cellular proliferation and survival. This compound may be useful in treating cancers associated with increased c-kit kinase activity.

scholarly journals (Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia

2021 ◽  
Vol 17 ◽  
pp. 2260-2269
Author(s):  
Luiz Claudio Ferreira Pimentel ◽  
Lucas Villas Boas Hoelz ◽  
Henayle Fernandes Canzian ◽  
Frederico Silva Castelo Branco ◽  
Andressa Paula de Oliveira ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Competitive Inhibition ◽  
Leukemia Cell ◽  
Docking Studies ◽  
Leukemia Cell Line ◽  
Inhibition Mechanism ◽  
Triazole Derivatives

The enzyme tyrosine kinase BCR-Abl-1 is the main molecular target in the treatment of chronic myeloid leukemia and can be competitively inhibited by tyrosine kinase inhibitors such as imatinib. New potential competitive inhibitors were synthesized using the (phenylamino)pyrimidine-pyridine (PAPP) group as a pharmacophoric fragment, and these compounds were biologically evaluated. The synthesis of twelve new compounds was performed in three steps and assisted by microwave irradiation in a 1,3-dipolar cycloaddition to obtain 1,2,3-triazole derivatives substituted on carbon C-4 of the triazole nucleus. All compounds were evaluated for their inhibitory activities against a chronic myeloid leukemia cell line (K562) that expresses the enzyme tyrosine kinase BCR-Abl-1 and against healthy cells (WSS-1) to observe their selectivity. Three compounds showed promising results, with IC50 values between 1.0 and 7.3 μM, and were subjected to molecular docking studies. The results suggest that such compounds can interact at the same binding site as imatinib, probably sharing a competitive inhibition mechanism. One compound showed the greatest interaction affinity for BCR-Abl-1 in the docking studies.

scholarly journals Octahydroquinoxalin-2(1H)-One-Based Aminophosphonic Acids and Their Derivatives—Biological Activity towards Cancer Cells

Materials ◽  
2020 ◽  
Vol 13 (10) ◽  
pp. 2393
Author(s):  
Jakub Iwanejko ◽  
Elżbieta Wojaczyńska ◽  
Eliza Turlej ◽  
Magdalena Maciejewska ◽  
Joanna Wietrzyk
Keyword(s):  
Cell Line ◽  
Mechanism Of Action ◽  
Caspase 3 ◽  
Antitumor Agents ◽  
Leukemia Cell ◽  
Mannich Bases ◽  
Leukemia Cell Line ◽  
Preliminary Evaluation ◽  
Aminophosphonic Acids ◽  
Low Cytotoxicity

In the search for new antitumor agents, aminophosphonic acids and their derivatives based on octahydroquinoxalin-2(1H)-one scaffold were obtained and their cytotoxic properties and a mechanism of action were evaluated. Phosphonic acid and phosphonate moieties increased the antiproliferative activity in comparison to phenolic Mannich bases previously reported. Most of the obtained compounds revealed a strong antiproliferative effect against leukemia cell line (MV-4-11) with simultaneous low cytotoxicity against normal cell line (mouse fibroblasts-BALB/3T3). The most active compound was diphenyl-[(1R,6R)-3-oxo-2,5-diazabicyclo[4.4.0]dec-4-yl]phosphonate. Preliminary evaluation of the mechanism of action showed the proapoptotic effect associated with caspase 3/7 induction.

scholarly journals Activation of the c-abl oncogene by viral transduction or chromosomal translocation generates altered c-abl proteins with similar in vitro kinase properties.

1985 ◽  
Vol 5 (1) ◽  
pp. 204-213 ◽  
Author(s):  
R L Davis ◽  
J B Konopka ◽  
O N Witte
Keyword(s):  
Tyrosine Kinase ◽  
Kinase Activity ◽  
Leukemia Virus ◽  
Leukemia Cell ◽  
Chromosomal Translocation ◽  
Leukemia Cell Line ◽  
Tyrosine Kinase Activity ◽  
Serine Kinase ◽  
Abelson Murine Leukemia Virus

The v-abl protein of Abelson murine leukemia virus is a tyrosine-specific kinase. Its normal cellular homolog, murine c-abl, does not possess detectable tyrosine kinase activity in vitro. Previously, we have detected tyrosine kinase activity in vitro for an altered c-abl gene product (c-abl P210) in the K562 human chronic myelogenous leukemia cell line. The expression of this variant c-abl gene product correlates with chromosomal translocation and amplification of the c-abl gene in K562 cells. Like v-abl, c-abl P210 is a fusion protein containing non-abl sequences near the amino terminus of c-abl. We compared the in vitro tyrosine kinase activity of c-abl P210 with that of wild-type murine v-abl. The remarkable similarities of these two proteins with respect to cis-acting autophosphorylation, trans-acting phosphorylation of exogenous substrates, and kinase inhibition, using site-directed abl-specific antisera, suggested that c-abl P210 could function similarly to v-abl in vivo. In addition, c-abl P210 possessed an associated serine kinase activity in immunoprecipitates. The serine kinase activity was not inhibited by site-directed, abl-specific antisera that inhibit the tyrosine kinase activity, suggesting that the serine kinase activity is not an intrinsic property of c-abl P210. Thus, the activation of the c-abl gene in a human leukemia cell line may have functional consequences analogous to activation of the c-abl gene in Abelson murine leukemia virus.

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