Polyoma virus middle t antigen antibody pymt scbt santa. Its study has led to the discovery of the roles of tyrosine kinase and phosphoinositide 3kinase pi3k signaling in mammalian growth control and transformation. P688351 fasta add to basket added to basket the sequence of this isoform can be found in the external entry p68835. The potent transforming activity of middle t antigen is dependent on its association with a number of cellular proteins such as members of the src family of protein kinase and the. Furthermore, replication of heterologous viruses such as vesicular stomatitis virus and. Polyoma virusinduced osteosarcomas in inbred strains of mice. We have purified the 36 and 63 kd cellular proteins known to associate with polyomavirus middle and small tumor t antigens and sv40 small t antigen. Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly. The polyoma virus t antigen interferes with interferon. The amino terminus of polyomavirus middle t antigen is. Male carriers develop mammary tumors with a later onset.
In order to understand the regulation of hiv genome transcription induced by cell stimulation through transmembrane receptors, we have transfected cells with polyoma middle t antigen pymt expression vectors, thus mimicking activated receptordependent cell. The insulinlike growth factor i receptor igfir and the. The polyoma middle t antigen pymt ag allows selective proliferation of ecs in. Plays a role in transformation by modulating the activities of cellular proteins involved in control of cell proliferation and by acting as a functional homolog of an activated tyrosine kinaseassociated growthfactor receptor. Consistent with the importance of erk2 activation for precommitment, ectopic expression of the a205 mutant of polyoma virus middle t antigen primes cells to differentiate in response to ra yen et al. Middle t antigen murine polyomavirus strain a2 mpyv. Association of p60 csrc with polyoma virus middlet antigen. An essential component of this action is a 22 amino. Previous studies have shown that the polyomavirusderived oncoprotein, middle t antigen mt, transforms rodent fibroblasts by interacting with and activating. The middle tumor antigen is a protein encoded in the genomes of some polyomaviruses, which. Additional lines produced include lines 121, 196, 235, 654, 668, 670. Endothelial cell transformation by polyomavirus middle t. In this investigation, we show that cell lines derived from wild type virusinduced breast tumors are resistant to the growth inhibitory action of interferon.
Dec 19, 2006 binding of src family kinases to membraneassociated polyoma virus middle t antigen pymt can result in the phosphorylation of pymt tyrosine 250, which serves as a docking site for the binding of shc and subsequent activation of the rafmekerk map kinase cascade. The polyomavirus middle t antigen pymt is an oncogene that activates the non receptor tyrosine kinase, csrc, and physically interacts with. Perturbed development of the mouse lens by polyomavirus. The middle t antigen of murine polyomavirus pymt rapidly transforms endothelial cells, leading to the formation of vascular tumors in newborn mice. The proximate biochemical response to tcr stimulation is the phosphorylation of several intracellular proteins on tyrosyl residues. The potent transforming activity of middle t antigen is dependent on its association with a number of cellular proteins such as members of the src family of protein kinase and the newly identified phosphatidylinositol kinase. The polyoma middle tantigen is used in animal breast cancer model systems like the pymt system where it ist coupled to the mmtv promotor. Polyoma virus, medium t antigen antibody pymt nb100. Polyoma and sv40 proteins differentially regulate pp2a to. These results support the hypothesis that fyn is involved in signal transduction events leading to il2 transcriptional activation in t cells. The polyomavirus middle tantigen oncogene activates the hippo. Polyoma virus middle t antigen pymt contains 421 amino acids and is divided into at least three domains, some of which are shared with pylt and polyoma virus small t antigen pyst.
Summary the small dna tumor viruses have provided a very longlived source of insights into many aspects of the life cycle of eukaryotic cells. Every product we sell is backed by novus 100% guarantee. There it functions as an oncogene, while the tissue where the tumor develops is determined by the mmtv promoter. In a screen for pymt variants that could not activate the arf tumor suppressor, we isolated a cytoplasmic nontransforming mutant. There are currently no images for polyoma virus, medium t antigen antibody nb1002749h. Courtneidge sa, smith ae 1984 the complex of polyoma virus middlet antigen and pp60 csrc. Lee, 1 and heiner westphap laboratory of molecular genetics, national institute of child health and development, and 2laboratory of. To address this question, we transfected polyoma virus middle t or small t alone or middle t and small t together into j3d mouse tlymphoma cells carrying temperaturesensitive p53 ts p53. The middle tumor antigen also called the middle t antigen and abbreviated mtag or mt is a protein encoded in the genomes of some polyomaviruses, which are small doublestranded dna viruses.
Activation of p60 csrc by middlet is accompanied both by. Identity was confirmed by comigration on twodimensional 2d gels and by 2d analysis of complete. In a screen for pymt variants that could not activate the arf tumor suppressor, we isolated a. Publications for polyoma virus, medium t antigen antibody nb10027498 we have publications tested in 1 confirmed species. The phospholipase plc and pld pathway activated by. Mt leads to the activation of cjun and cfos promoters 262, 301. Lessons in signaling and tumorigenesis from polyomavirus middle. Abstract binding of src family kinases to membraneassociated polyoma virus middle t antigen pymt can result in the phosphorylation of pymt tyrosine 250, which serves as a docking site for the binding of shc and subsequent activation of the rafmekerk map kinase cascade. Physical and functional interaction between polyoma virus. The polyomavirus middle t antigen pymt is an oncogene that activates the nonreceptor tyrosine kinase, csrc, and physically interacts with taz wwtr1. Polyoma small and middle t antigens and sv40 small t. Expression of the polyoma virus middle t antigen in hl60 cells accelerates their differentiation in response to both monocytic and granulocytic differentiationinducing agents. Mtag is expressed early in the infectious cycle along with two other related proteins, the small tumor antigen and large tumor antigen.
Polyomaviridae is a family of viruses whose natural hosts are primarily mammals and birds. In recent years, the emphasis has been on cancerrelated signaling. Source polyoma virus middle t antigen pymt is a rat. Expression of polyomavirus middle t antigen pymt rapidly induces endothelial tumors hemangiomas in mice, with an apparent single ratelimiting step. There it functions as an oncogene, while the tissue where the tumor develops is determined by the mmtv promotor. To investigate whether the serinethreonine kinase aktpkb, which is the protooncogene transduced by the transforming akt8 retrovirus, is activated by pmt, 3t3l1 fibroblasts were stably transfected with wild type pmt. Transformation with the polyoma middle t antigen also activates lipid signaling and the classical mitogenic pathway 44. Natural biology of polyomavirus middle t antigen ncbi nih. Pdf urokinase type plasminogen activator gene regulation by.
Pmt expression accelerated glucose transport and increased. Middletassociated as well as uncomplexed pp60csrc is predominantly found in the plasma membrane. Middle t associated as well as uncomplexed pp60csrc is predominantly found in the plasma membrane. Polyoma middle t antigen pmt was originally identified as the tumorigenic component of the polyomavirus genome. G higgins3,5, brian s schaffhausen4, and thomas m roberts1,2 1department of cancer biology, danafarber cancer institute 2department of biological chemistry and molecular. Wildtype polyoma virus infection led to a 3fold increase in the rate of 2deoxyglucose 2dg uptake, whereas a weakly transforming polyoma virus mutant that. Polyoma virus, medium t antigen antibody pymt nb1002749. The polyomavirus middle tantigen oncogene activates the. Polyomavirus middle tantigen is a transmembrane protein that.
Middle t antigen middle t, the transforming gene product of polyomavirus, associates with several cellular tyrosine kinases, such as pp60csrc. Phosphorylation of polyoma middle t antigen and cellular proteins in purified plasma membranes of polyoma virusinfected cells. Middle t associates with and thereby activates p60 csrc, a cellular tyrosine kinase homologous to the oncogene product of rous sarcoma virus 2,3. Kramer, in signal transduction third edition, 2016. Polyoma virus middle t antigen pyvmt is a powerful viral oncogene. Middle t antigen pymt is the principal transforming component of polyomavirus, and rapidly induces hemangiomas in neonatal mice. Polyoma middle t antigen pi3 kinase tyrosine kinase signal transduction cancer middle tantigen mt is the principal oncogene of murine polyomavirus. Identity was confirmed by comigration on twodimensional 2d gels and by 2d analysis of. The rhoa activating protein net1 contributes to breast cancer cell proliferation, motility, and invasion in vitro, yet little is known about its roles in mammary gland tumorigenesis and metastasis. Pyvt, polyoma virus middle t antigen, polyoma virus. Jul 20, 2009 polyoma virus middle t antigen pyvmt is a powerful viral oncogene. Abstract binding of src family kinases to membraneassociated polyoma virus middle tantigen pymt can result in the phosphorylation of pymt tyrosine 250, which serves as a docking site for the binding of shc and subsequent activation of the rafmekerk map kinase cascade.
Each of these agents is known to be able to prime hl60 cells and accelerate subsequently induced myeloid or monocytic differentiation and g0 cell cycle arrest. Polyoma middle t antigen activates the serthr kinase akt. Reduced metastasis of polyoma virus middle t antigen induced mammary cancer in plasminogendeficient mice. Binding of src family kinases to membraneassociated polyoma virus middle tantigen pymt can result in the phosphorylation of pymt tyrosine 250, which serves as a docking site for the binding of shc and subsequent activation of the rafmekerk map kinase cascade. Furthermore, replication of heterologous viruses such as vesicular stomatitis virus and encephalomyocarditis virus was. Association of p60 csrc with polyoma virus middlet. Lessons in signaling and tumorigenesis from polyomavirus. Effective in vivo models of breast cancer are crucial for studying the development and progression of the disease in humans. Yen a1, cherington v, schaffhausen b, marks k, varvayanis s. Because activation of srclike kinases is thought to be an important component of pymtinduced transformation, we have analyzed the functional requirement for individual kinases in this process. Activation of p60 csrc by middle t is accompanied both by. Pymt is a major transforming protein responsible for inducing the phenotype of transformed cells and, without it, transformation does not occur.
Phosphatidylinositol 3kinase binding to polyoma virus. This transgene expresses polyoma virus middle t antigen under the control of the mouse mammary tumor. As of the most recent 2018 taxonomy release by the international committee on taxonomy of viruses, there were 89 recognized species in this family contained within four genera, as well as 9 species that could not be assigned to a genus. Polyoma small and middle t antigens and sv40 small t antigen. Polyomavirus middle t antigen as a probe for t cell. Net1 knockout ko mice were bred to mice with mammary gland specific expression of the polyoma middle t antigen pymt oncogene. Phosphatidylinositol 3kinase binding to polyoma virus middle. Polyoma small t antigen triggers cell death via mitotic catastrophe arun t pores fernando1,2,6, shaida andrabi1,6,7, onur cizmecioglu1,2, cailei zhu3, david m. Myristylation of pp60csrc is not required for complex. Contributions of the rhoa guanine nucleotide exchange factor. Virus middle t antigen an overview sciencedirect topics.
Microbiology and tumor biology center, karolinska institute, s171 77 stockholm, sweden abstract. Mmtvpymt mmtvpyvmt females develop palpable mammary tumors which metastasize to the lung. Mammary gland tumorigenesis and lung metastasis were monitored. The middle t antigen, the major viral transforming protein, activates multiple signal transduction pathways essential for tumor induction.
Polyoma virus small t antigen enhances replication of viral genomes in 3t6 mouse fibroblasts. Wildtype p53 triggers two distinct biological responses, cell cycle arrest and apoptosis. The middle tumor antigen is used in model organisms developed to study cancer, such as the mmtvpymt system where middle t is coupled to the mmtv promoter. Middle t antigen murine polyomavirus strain bg mpyv. The middle tumor antigen middlet of mouse polyomavirus is responsible for the transforming potential of this virus. Transgenic mice expressing middle t under control of the mouse mammary tumor virus regulatory region develop mammary tumors which metastasize to the lung 16. Middlet associates with and thereby activates p60 csrc, a cellular tyrosine kinase homologous to the oncogene product of rous sarcoma virus 2,3. Middlet associates with and thereby activates p60 csrc, a cellular tyrosine kinase homologous to.
Urokinase type plasminogen activator gene regulation by. In polyomavirustransformed cells, pp60csrc is activated by association with polyomavirus middle t antigen. Wildtype polyoma virus infection led to a 3fold increase in the rate of 2deoxyglucose 2dg uptake, whereas a weakly. Murine polyoma virus mpyv is a small dna virus that induces tumors in multiple tissues of infected host. Genetic analyses have revealed that the carboxyterminal. Middlet antigen middlet, the transforming gene product of polyomavirus, associates with several cellular tyrosine kinases, such as pp60csrc. Polyoma virusinduced osteosarcomas in inbred strains of. Association of p60csrc with polyoma virus middlet antigen. Polyoma middle t antigen activates the serthr kinase akt in. Polyoma definition of polyoma by the free dictionary. Protein kinase bakt is activated by polyomavirus middlet antigen. We sought to engineer a novel mouse model of polyomavirus middle t antigen pyv mtmediated mammary tumourigenesis in which inducible expression of this wellcharacterized viral oncoprotein is coupled to cre recombinase teto. Binding of polyoma virus large t antigen to the human hsp 70 promoter is not required fortrans activation. Middle t expressing cells treated with the granulocytic inducer retinoic acid or the monocytic inducer 1,25dihydroxy vitamin d3 differentiated 24 h earlier than parental, mockelectroporated, or vector control cell.
Murine polyomavirus middle tantigen mt induces tumors by mimicking an activated growth factor receptor. Their activation sets off a series of signaling cascades. Middle texpressing cells treated with the granulocytic inducer retinoic acid or the monocytic inducer 1,25dihydroxy vitamin d3 differentiated 24 h earlier than parental, mockelectroporated, or vector control cell. Finally, the activation of il2 transcription by hamt and not by momt shown here parallels the ability of the. In order to understand the regulation of hiv genome transcription induced by cell stimulation through transmembrane receptors, we have transfected cells with polyoma middle t antigen pymt expression vectors, thus mimicking activated receptordependent cell stimulation. Inducible and coupled expression of the polyomavirus. Lessons from polyoma middle t antigen on signaling and.
Polyoma virus middle t and small t antigens cooperate to antagonize p53induced cell cycle arrest and apoptosis 1 wang qian and klas g. The a205 mutant is a deletion mutant of the polyoma middle t antigen, the transforming agent of polyoma virus. Microsequencing of the 36 kd protein indicated that it was probably identical to the catalytic subunit of protein phosphatase 2a pp2a. Transformationdefective polyoma middle t antigen mutants defective in plcgamma, pi3, or src kinase activation enhance erk2 activation and promote retinoic acidinduced, cell differentiation like wildtype middle t. It first caught attention as being a protein associated with the polyoma middle t antigen whitman et al. Recruits upon association with host ppp2pp2a the src tyrosine kinase components src, yes and fyn, thereby activating their kinase activity. Induction of interleukin2 transcription by the hamster. These mice express the polyoma virus middle t antigen under the direction of the mouse mammary tumor virus promoterenhancer and may be suitable for use in studies. For example, mtag binds and activates srcfamily protein tyrosine kinases in a.
Engagement of the multisubunit t cell antigen receptor tcr1 complex triggers a cascade of intracellular signaling events that culminate in the activation and proliferation of t lymphocytes 1, 2. The polyoma middle t antigen is used in animal breast cancer model systems like the pymt system where it ist coupled to the mmtv promotor. Mutation of a cysteine residue in polyomavirus middle t antigen abolishes interactions with protein phosphatase 2a, pp60 csrc, and phosphatidylinositol3 kinase, activation of cfos expression, and cellular transformation. Elevation in the rate of glucose transport in polyoma virusinfected mouse fibroblasts was dependent upon phosphatidylinositol 3kinase pi 3kinase. Polyoma virus middle t and small t antigens cooperate to. Transformationdefective polyoma middle t antigen mutants. Contributions of the rhoa guanine nucleotide exchange. Polyoma small t antigen triggers cell death via mitotic. Perturbed development of the mouse lens by polyomavirus large t antigen does not lead to tumor formation anne e. Unlike sv40 large t, polyoma virus large t does not bind p53, and it is still unclear how polyoma virus blocks p53 function. Polyomavirus middle t antigen as a probe for t cell antigen. Polyoma virus, medium t antigen antibody pymt hrp nb100. Mechanism of activation of complexed pp60csrc by the middle. Relevance of the plasminogen activation system in the pathogenesis and progression of gastric cancer.
P0doj42 fasta add to basket added to basket the sequence of this isoform can be found in the external entry p0doj4. May 01, 1999 transformationdefective polyoma middle t antigen mutants defective in plcgamma, pi3, or src kinase activation enhance erk2 activation and promote retinoic acidinduced, cell differentiation like wildtype middle t. The phospholipase plc and pld pathway activated by rtk, results in the. These complexes have a higher tyrosine kinase activity compared with that of unassociated pp60csrc. Complex formation leads to kinase activation and is essential for cell transformation. Hiv genome transcription induced by polyoma virus middle t.
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