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1.
Phys Rev Lett ; 119(4): 046802, 2017 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-29341777

RESUMO

In this work we perform direct single-shot readout of the singlet-triplet states in exchange coupled electrons confined to precision-placed donor atoms in silicon. Our method takes advantage of the large energy splitting given by the Pauli-spin blockaded (2,0) triplet states, from which we can achieve a single-shot readout fidelity of 98.4±0.2%. We measure the triplet-minus relaxation time to be of the order 3 s at 2.5 T and observe its predicted decrease as a function of magnetic field, reaching 0.5 s at 1 T.

2.
Phys Rev Lett ; 118(13): 130503, 2017 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-28409950

RESUMO

A boson-sampling device is a quantum machine expected to perform tasks intractable for a classical computer, yet requiring minimal nonclassical resources as compared to full-scale quantum computers. Photonic implementations to date employed sources based on inefficient processes that only simulate heralded single-photon statistics when strongly reducing emission probabilities. Boson sampling with only single-photon input has thus never been realized. Here, we report on a boson-sampling device operated with a bright solid-state source of single-photon Fock states with high photon-number purity: the emission from an efficient and deterministic quantum dot-micropillar system is demultiplexed into three partially indistinguishable single photons, with a single-photon purity 1-g^{(2)}(0) of 0.990±0.001, interfering in a linear optics network. Our demultiplexed source is between 1 and 2 orders of magnitude more efficient than current heralded multiphoton sources based on spontaneous parametric down-conversion, allowing us to complete the boson-sampling experiment faster than previous equivalent implementations.

3.
Phys Rev Lett ; 112(14): 143603, 2014 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-24765961

RESUMO

Holonomic phases--geometric and topological--have long been an intriguing aspect of physics. They are ubiquitous, ranging from observations in particle physics to applications in fault tolerant quantum computing. However, their exploration in particles sharing genuine quantum correlations lacks in observations. Here, we experimentally demonstrate the holonomic phase of two entangled photons evolving locally, which, nevertheless, gives rise to an entanglement-dependent phase. We observe its transition from geometric to topological as the entanglement between the particles is tuned from zero to maximal, and find this phase to behave more resiliently to evolution changes with increasing entanglement. Furthermore, we theoretically show that holonomic phases can directly quantify the amount of quantum correlations between the two particles. Our results open up a new avenue for observations of holonomic phenomena in multiparticle entangled quantum systems.

4.
Phys Rev Lett ; 111(23): 230504, 2013 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-24476241

RESUMO

The key requirement for quantum networking is the distribution of entanglement between nodes. Surprisingly, entanglement can be generated across a network without direct transfer-or communication-of entanglement. In contrast to information gain, which cannot exceed the communicated information, the entanglement gain is bounded by the communicated quantum discord, a more general measure of quantum correlation that includes but is not limited to entanglement. Here, we experimentally entangle two communicating parties sharing three initially separable photonic qubits by exchange of a carrier photon that is unentangled with either party at all times. We show that distributing entanglement with separable carriers is resilient to noise and in some cases becomes the only way of distributing entanglement through noisy environments.

5.
Opt Express ; 19(23): 22698-708, 2011 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-22109151

RESUMO

We present a simple technique to reduce the emission rate of higher-order photon events from pulsed spontaneous parametric down-conversion. The technique uses extra-cavity control over a mode locked ultrafast laser to simultaneously increase repetition rate and reduce the energy of each pulse from the pump beam. We apply our scheme to a photonic quantum gate, showing improvements in the non-classical interference visibility for 2-photon and 4-photon experiments, and in the quantum-gate fidelity and entangled state production in the 2-photon case.

6.
Phys Rev Lett ; 106(10): 100401, 2011 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-21469772

RESUMO

The resources required to characterize the dynamics of engineered quantum systems--such as quantum computers and quantum sensors--grow exponentially with system size. Here we adapt techniques from compressive sensing to exponentially reduce the experimental configurations required for quantum process tomography. Our method is applicable to processes that are nearly sparse in a certain basis and can be implemented using only single-body preparations and measurements. We perform efficient, high-fidelity estimation of process matrices of a photonic two-qubit logic gate. The database is obtained under various decoherence strengths. Our technique is both accurate and noise robust, thus removing a key roadblock to the development and scaling of quantum technologies.


Assuntos
Força Compressiva , Teoria Quântica , Fótons
7.
Phys Rev Lett ; 104(15): 153602, 2010 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-20481989

RESUMO

Quantum walks have a host of applications, ranging from quantum computing to the simulation of biological systems. We present an intrinsically stable, deterministic implementation of discrete quantum walks with single photons in space. The number of optical elements required scales linearly with the number of steps. We measure walks with up to 6 steps and explore the quantum-to-classical transition by introducing tunable decoherence. Finally, we also investigate the effect of absorbing boundaries and show that decoherence significantly affects the probability of absorption.

8.
Nat Commun ; 9(1): 980, 2018 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-29515115

RESUMO

Substitutional donor atoms in silicon are promising qubits for quantum computation with extremely long relaxation and dephasing times demonstrated. One of the critical challenges of scaling these systems is determining inter-donor distances to achieve controllable wavefunction overlap while at the same time performing high fidelity spin readout on each qubit. Here we achieve such a device by means of scanning tunnelling microscopy lithography. We measure anti-correlated spin states between two donor-based spin qubits in silicon separated by 16 ± 1 nm. By utilising an asymmetric system with two phosphorus donors at one qubit site and one on the other (2P-1P), we demonstrate that the exchange interaction can be turned on and off via electrical control of two in-plane phosphorus doped detuning gates. We determine the tunnel coupling between the 2P-1P system to be 200 MHz and provide a roadmap for the observation of two-electron coherent exchange oscillations.

9.
Mol Cell Biol ; 17(3): 1702-13, 1997 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9032297

RESUMO

The focal adhesion kinase (FAK), a protein-tyrosine kinase (PTK), associates with integrin receptors and is activated by cell binding to extracellular matrix proteins, such as fibronectin (FN). FAK autophosphorylation at Tyr-397 promotes Src homology 2 (SH2) domain binding of Src family PTKs, and c-Src phosphorylation of FAK at Tyr-925 creates an SH2 binding site for the Grb2 SH2-SH3 adaptor protein. FN-stimulated Grb2 binding to FAK may facilitate intracellular signaling to targets such as ERK2-mitogen-activated protein kinase. We examined FN-stimulated signaling to ERK2 and found that ERK2 activation was reduced 10-fold in Src- fibroblasts, compared to that of Src- fibroblasts stably reexpressing wild-type c-Src. FN-stimulated FAK phosphotyrosine (P.Tyr) and Grb2 binding to FAK were reduced, whereas the tyrosine phosphorylation of another signaling protein, p130cas, was not detected in the Src- cells. Stable expression of residues 1 to 298 of Src (Src 1-298, which encompass the SH3 and SH2 domains of c-Src) in the Src- cells blocked Grb2 binding to FAK; but surprisingly, Src 1-298 expression also resulted in elevated p130cas P.Tyr levels and a two- to threefold increase in FN-stimulated ERK2 activity compared to levels in Src- cells. Src 1-298 bound to both FAK and p130cas and promoted FAK association with p130cas in vivo. FAK was observed to phosphorylate p130cas in vitro and could thus phosphorylate p130cas upon FN stimulation of the Src 1-298-expressing cells. FAK-induced phosphorylation of p130cas in the Src 1-298 cells promoted the SH2 domain-dependent binding of the Nck adaptor protein to p130cas, which may facilitate signaling to ERK2. These results show that there are additional FN-stimulated pathways to ERK2 that do not involve Grb2 binding to FAK.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Moléculas de Adesão Celular/metabolismo , Fibronectinas/farmacologia , Fosfoproteínas/metabolismo , Proteínas Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas pp60(c-src)/metabolismo , Transdução de Sinais/fisiologia , Animais , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Células Cultivadas , Proteína Substrato Associada a Crk , Ativação Enzimática , Fibroblastos , Quinase 1 de Adesão Focal , Proteína-Tirosina Quinases de Adesão Focal , Proteína Adaptadora GRB2 , Integrinas/fisiologia , Camundongos , Camundongos Knockout , Proteína Quinase 1 Ativada por Mitógeno , Proteínas Oncogênicas/metabolismo , Mapeamento de Peptídeos , Fosforilação , Proteínas/metabolismo , Proteína p130 Retinoblastoma-Like , Domínios de Homologia de src
10.
Mol Cell Biol ; 20(23): 9018-27, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11074000

RESUMO

The use of small-molecule inhibitors to study molecular components of cellular signal transduction pathways provides a means of analysis complementary to currently used techniques, such as antisense, dominant-negative (interfering) mutants and constitutively activated mutants. We have identified and characterized a small-molecule inhibitor, SU6656, which exhibits selectivity for Src and other members of the Src family. A related inhibitor, SU6657, inhibits many kinases, including Src and the platelet-derived growth factor (PDGF) receptor. The use of SU6656 confirmed our previous findings that Src family kinases are required for both Myc induction and DNA synthesis in response to PDGF stimulation of NIH 3T3 fibroblasts. By comparing PDGF-stimulated tyrosine phosphorylation events in untreated and SU6656-treated cells, we found that some substrates (for example, c-Cbl, and protein kinase C delta) were Src family substrates whereas others (for example, phospholipase C-gamma) were not. One protein, the adaptor Shc, was a substrate for both Src family kinases (on tyrosines 239 and 240) and a distinct tyrosine kinase (on tyrosine 317, which is perhaps phosphorylated by the PDGF receptor itself). Microinjection experiments demonstrated that a Shc molecule carrying mutations of tyrosines 239 and 240, in conjunction with an SH2 domain mutation, interfered with PDGF-stimulated DNA synthesis. Deletion of the phosphotyrosine-binding domain also inhibited synthesis. These inhibitions were overcome by heterologous expression of Myc, supporting the hypothesis that Shc functions in the Src pathway. SU6656 should prove a useful additional tool for further dissecting the role of Src kinases in this and other signal transduction pathways.


Assuntos
Ubiquitina-Proteína Ligases , Quinases da Família src/antagonistas & inibidores , Células 3T3 , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Indóis/farmacologia , Concentração Inibidora 50 , Isoenzimas/metabolismo , Camundongos , Mitose/efeitos dos fármacos , Fator de Crescimento Derivado de Plaquetas/farmacologia , Proteína Quinase C/metabolismo , Proteína Quinase C-delta , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-cbl , Proteínas Proto-Oncogênicas c-myc/biossíntese , Receptores do Fator de Crescimento Derivado de Plaquetas/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Sulfonamidas/farmacologia
11.
Oncogene ; 14(1): 17-34, 1997 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-9010229

RESUMO

Treatment of quiescent NIH3T3 cells with PDGF BB results in the transient activation and hyperphosphorylation of the protein-tyrosine kinase, c-Src. These effects correlate with novel serine and tyrosine phosphorylations in the N-terminal non-catalytic region of the molecule, which contains an SH3 and SH2 domain. In this study, a site of PDGF-induced tyrosine phosphorylation was mapped to Tyr 138 in the SH3 domain; Tyr 138 is exposed on the SH3 peptide binding surface. This same site is phosphorylated in vitro by the PDGF receptor when purified baculovirus-expressed c-Src is complexed with the activated receptor. Phosphorylation of Tyr 138 required association of c-Src with the PDGF receptor via its SH2 domain. When a c-Src Phe 138 mutant was stably expressed in Src- mouse fibroblasts, it was activated to the same extent as wild type c-Src following PDGF stimulation, indicating that phosphorylation of this site is not required for PDGF-mediated activation. However, Tyr 138 phosphorylation was found to diminish SH3 domain peptide ligand binding ability in vitro.


Assuntos
Fator de Crescimento Derivado de Plaquetas/farmacologia , Proteínas Tirosina Quinases/metabolismo , Receptores do Fator de Crescimento Derivado de Plaquetas/metabolismo , Tirosina/metabolismo , Domínios de Homologia de src , Células 3T3 , Sequência de Aminoácidos , Animais , Proteína Tirosina Quinase CSK , Células Cultivadas , Camundongos , Dados de Sequência Molecular , Mapeamento de Peptídeos , Fosforilação , Proteínas Tirosina Quinases/genética , Proteínas Tirosina Quinases/isolamento & purificação , Proteínas Recombinantes/isolamento & purificação , Alinhamento de Sequência , Spodoptera , Domínios de Homologia de src/fisiologia , Quinases da Família src
12.
Oncogene ; 19(24): 2867-9, 2000 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-10851090

RESUMO

A growing body of literature suggests that the ubiquitously expressed Src family kinases (Src, Fyn and Yes) are required for agents such as platelet-derived growth factor (PDGF) to stimulate DNA synthesis. Yet Klinghoffer and colleagues recently presented evidence that fibroblasts derived from mice null for Src, Fyn and Yes responded normally to PDGF (Klinghoffer et al., 1999, EMBO J., 18: 2459 - 2471). What is the reason for this discrepancy? We noted that Klinghoffer et al. (1999) used SV40 large T antigen (largeT) to facilitate derivation of cell lines from the embryos. We therefore tested the effect of largeT on PDGF receptor signaling. We found that expression of largeT overcame the inhibitory effects of interfering forms of both Ras (N17Ras) and Src (SrcK-). Furthermore, injection of SrcK- or the cst.1 antibody (which inhibits Src, Fyn and Yes) failed to inhibit PDGF-stimulated DNA synthesis in NIH3T3 cells expressing dominant negative p53, and fibroblasts derived from p53 null embryos. These data suggest firstly that caution should be used in interpretation of experiments conducted in cell lines expressing largeT, and secondly that the role of Src family kinases in growth factor signaling may be to oppose the effects of negative growth regulators such as p53. Oncogene (2000) 19, 2867 - 2869


Assuntos
Antígenos Transformantes de Poliomavirus/fisiologia , Fator de Crescimento Derivado de Plaquetas/farmacologia , Quinases da Família src/fisiologia , Células 3T3 , Animais , Bromodesoxiuridina/metabolismo , DNA/biossíntese , Fibroblastos/fisiologia , Camundongos , Proteína Supressora de Tumor p53/fisiologia
13.
Oncogene ; 18(18): 2908-12, 1999 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-10362262

RESUMO

In C. elegans, genetic and biochemical data indicate that the Cbl homolog Sli-1 attenuates Let-23 (EGFR) signaling. To investigate whether c-Cbhl might have a role in mammalian growth factor-mediated mitogenic signaling, we microinjected NIH3T3 mouse fibroblasts with expression plasmids encoding wt and G306ECbl (a 'loss of function' mutant identified in C. elegans). We observed inhibition of PDGF BB- and EGF-induced DNA synthesis by wt Cbl but not the mutant. Microinjection of two different affinity purified polyclonal antisera against Cbl boosted a suboptimal PDGF-stimulated mitogenic response. The inhibition of both PDGF BB- and EGF-induced DNA synthesis by wt Cbl was reversed by co-expression with Myc but not with Fos. DNA synthesis initiated by constitutively activated Src was also blocked by Cbl expression, but curiously by the G306E mutant as well. These data are all consistent with the proposition that Cbl negatively affects mitogenic signaling in mammalian fibroblasts.


Assuntos
Citoplasma/enzimologia , DNA/biossíntese , Proteínas Proto-Oncogênicas/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Ubiquitina-Proteína Ligases , Células 3T3/efeitos dos fármacos , Células 3T3/metabolismo , Animais , Bromodesoxiuridina/metabolismo , Linhagem Celular , Fator de Crescimento Epidérmico/metabolismo , Fator de Crescimento Epidérmico/farmacologia , Genes fos , Genes myc , Genes src , Hemaglutininas/genética , Hemaglutininas/metabolismo , Humanos , Soros Imunes , Immunoblotting , Camundongos , Mutação , Fator de Crescimento Derivado de Plaquetas/metabolismo , Fator de Crescimento Derivado de Plaquetas/farmacologia , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/imunologia , Proteínas Proto-Oncogênicas c-cbl , Coelhos , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Transdução de Sinais
14.
J Biol Chem ; 271(28): 16798-806, 1996 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-8663329

RESUMO

The Src family protein-tyrosine kinases are required for mitogenic signaling from the platelet-derived growth factor (PDGF), colony stimulating factor-1, and epidermal growth factor (EGF) receptor protein-tyrosine kinases (RPTK) (Twamley-Stein, G. M., Pepperkok, R., Ansorge, W., and Courtneidge, S. A. (1993) Proc. Natl. Acad. Sci. U. S. A. 90, 7696-7700; Roche, S., Koegl, M., Barone, M. V., Roussel, M. F., and Courtneidge, S. A.(1995) Mol. Cell. Biol. 15, 1102-1109). In NIH3T3 fibroblasts, c-Src, Fyn, and c-Yes associate with the activated PDGF receptor, are substrates for receptor phosphorylation, and are themselves activated. Src family catalytic function is required for RPTK mitogenic signaling as evidenced by the SH2-dependent dominant negative phenotype exhibited by kinase-inactive Src and Fyn mutants (Twamley-Stein, G. M., Pepperkok, R., Ansorge, W., and Courtneidge, S. A.(1993) Proc. Natl. Acad. Sci. U. S. A. 90, 7696-7700). Here, we have generated clonal Src- murine fibroblast cell lines overexpressing various murine c-Src mutants and studied the effect of these mutant Src proteins on PDGF- and EGF-induced mitogenesis. Two c-Src SH3 domain mutants, Y133F and Y138F, each inhibited PDGF BB- and EGF-induced DNA synthesis in quiescent cells. This demonstrates an involvement of the Src SH3 domain in PDGFbeta and EGF receptor mitogenic signaling. Since both Tyr-133 and Tyr-138 are located on the ligand binding surface of the SH3 domain, these results suggest that the c-Src SH3 domain is required for PDGF and EGF mitogenic signaling. The dominant negative effect of either single mutant on PDGF receptor signaling was reversed by a second SH2-inactivating mutation. We conclude that the c-Src SH3 domain function requires the SH2 domain in the case of the PDGF receptor, presumably because binding of c-Src to the receptor via its SH2 domain is a prerequisite for the SH3 domain function. In contrast, SH2 function is apparently not essential for the SH3 function in EGF receptor signaling.


Assuntos
Fator de Crescimento Epidérmico/metabolismo , Mitógenos/metabolismo , Fator de Crescimento Derivado de Plaquetas/metabolismo , Proteínas Proto-Oncogênicas pp60(c-src)/metabolismo , Transdução de Sinais , Domínios de Homologia de src , Células 3T3 , Animais , Sequência de Bases , Becaplermina , Catálise , Linhagem Celular Transformada , Células Clonais , Clonagem Molecular , Camundongos , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Oligodesoxirribonucleotídeos , Proteínas Proto-Oncogênicas c-sis , Proteínas Proto-Oncogênicas pp60(c-src)/genética
15.
J Biol Chem ; 269(26): 17593-9, 1994 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-8021267

RESUMO

The Arabidopsis Atpk1 protein expressed in insect cells and plant cells exhibited multiple sizes consisting mainly of two doublets: p70 (68 and 70 kDa) and p85 (82 and 85 kDa). Extraction of p85 from cells required the presence of SDS, suggesting that p85 is associated with less soluble subcellular components. p70 was extracted by nonionic detergent without SDS, indicating that this form is cytoplasmic. p70 expressed in either Arabidopsis or insect cells underwent serine-specific autophosphorylation, indicating that Atpk1 is a protein-serine kinase. A point mutation (lysine 163 to arginine) in the ATP-binding site of the catalytic domain substantially diminished activity when expressed in insect cells. A 14-kDa protein (p14) was co-immunoprecipitated with p70 from insect cells expressing wild-type Atpk1 and was phosphorylated in immune complex kinase assays with Atpk1, suggesting it is a homolog of a natural substrate of Atpk1. Two plant ribosomal proteins (14 and 16 kDa) can be phosphorylated by the Atpk1 protein kinase, and we propose that Atpk1 is a novel ribosomal protein kinase. A 60-kDa form of Atpk1 derived from the insect cell-expressed p70 was more highly phosphorylated than p70 in in vitro kinase assays, suggesting a negative regulatory domain can be removed by proteolysis.


Assuntos
Proteínas de Arabidopsis , Arabidopsis/enzimologia , Proteínas de Plantas/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Ribossomos/enzimologia , Animais , Baculoviridae/genética , Células Cultivadas , Clonagem Molecular , Ativação Enzimática , Genes de Plantas , Hidrólise , Mariposas , Proteínas de Plantas/genética , Processamento de Proteína Pós-Traducional , Proteínas Serina-Treonina Quinases/genética , Especificidade por Substrato
16.
J Biol Chem ; 268(24): 18070-5, 1993 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-7688738

RESUMO

A current model for the regulation of the Src protein-tyrosine kinase proposes that the COOH-terminal phosphotyrosine, Tyr-527, binds to the Src homology 2 (SH2) region in an intramolecular interaction that represses the kinase domain. This model is consistent with the activation of Src by mutations in the SH2 domain or COOH terminus. Mutations in the SH3 domain also activate Src, although this region is not thought to bind phosphotyrosine. Seidel-Dugan et al. (Seidel-Dugan, C., Meyer, B. E., Thomas, S. M., and Brugge, J. S. (1992) Mol. Cell. Biol. 12, 1835-1845) have shown that Src mutants with deletions in the SH2 or SH3 domain transform chicken embryo fibroblasts and have increased kinase activity. These mutant proteins are underphosphorylated at Tyr-527, a change that could in itself activate the mutants. Therefore, it is not possible to distinguish whether the SH2 and SH3 domains are needed for phosphorylation of Tyr-527 or for Src to adopt or maintain the repressed state. We have artificially increased the level of Tyr-527 phosphorylation of SH2 and SH3 deletion mutants by coexpressing them with the Tyr-527 kinase, Csk, in yeast cells. We find that both the SH2 and SH3 domains are needed for inhibition of Src by Csk. The SH2 domain is needed for efficient phosphorylation by Csk, both in yeast cells and in vitro. The SH3 domain is needed for Src to be inhibited when Tyr-527 is phosphorylated by Csk. This suggests that the SH3 domain cooperates with the SH2 domain and phosphorylated Tyr-527 to inhibit the kinase domain. Dephosphorylation of SH3 domain mutants at Tyr-527 in fibroblasts could be a consequence of a failure of the proposed SH2/phosphotyrosine interaction.


Assuntos
Genes src , Proteína Oncogênica pp60(v-src)/metabolismo , Proteínas Tirosina Quinases/metabolismo , Tirosina , Animais , Proteína Tirosina Quinase CSK , Embrião de Galinha , Fibroblastos , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Mutagênese Sítio-Dirigida , Proteína Oncogênica pp60(v-src)/genética , Proteína Oncogênica pp60(v-src)/isolamento & purificação , Fosfotirosina , Proteínas Tirosina Quinases/genética , Proteínas Tirosina Quinases/isolamento & purificação , Proteínas Recombinantes de Fusão/isolamento & purificação , Proteínas Recombinantes de Fusão/metabolismo , Mapeamento por Restrição , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Deleção de Sequência , Transformação Genética , Tirosina/análogos & derivados , Tirosina/metabolismo , Quinases da Família src
17.
Proc Natl Acad Sci U S A ; 98(13): 7319-24, 2001 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-11404481

RESUMO

Signal transducer and activator of transcription (STAT) proteins perform key roles in mediating signaling by cytokines and growth factors, including platelet-derived growth factor (PDGF). In addition, Src family kinases activate STAT signaling and are required for PDGF-induced mitogenesis in normal cells. One STAT family member, Stat3, has been shown to have an essential role in cell transformation by the Src oncoprotein. However, the mechanisms by which STAT-signaling pathways contribute to mitogenesis and transformation are not fully defined. We show here that disruption of Stat3 signaling by using dominant-negative Stat3beta protein in NIH 3T3 fibroblasts suppresses c-Myc expression concomitant with inhibition of v-Src-induced transformation. Ectopic expression of c-Myc is able to partially reverse this inhibition, suggesting that c-Myc is a downstream effector of Stat3 signaling in v-Src transformation. Furthermore, c-myc gene knockout fibroblasts are refractory to transformation by v-Src, consistent with a requirement for c-Myc protein in v-Src transformation. In normal NIH 3T3 cells, disruption of Stat3 signaling with dominant-negative Stat3beta protein inhibits PDGF-induced mitogenesis in a manner that is reversed by ectopic c-Myc expression. Moreover, inhibition of Src family kinases with the pharmacologic agent, SU6656, blocks Stat3 activation by PDGF. These findings, combined together, delineate the signaling pathway, PDGF --> Src --> Stat3 --> Myc, that is important in normal PDGF-induced mitogenesis and subverted in Src transformation.


Assuntos
Divisão Celular/fisiologia , Transformação Celular Neoplásica , Proteínas de Ligação a DNA/metabolismo , Regulação da Expressão Gênica , Genes src , Fator de Crescimento Derivado de Plaquetas/farmacologia , Proteínas Proto-Oncogênicas c-myc/genética , Transativadores/metabolismo , Células 3T3 , Animais , Divisão Celular/efeitos dos fármacos , Linhagem Celular Transformada , Transformação Celular Neoplásica/efeitos dos fármacos , Genes myc , Camundongos , Modelos Biológicos , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Recombinantes/metabolismo , Fator de Transcrição STAT3 , Transdução de Sinais
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