Association of phosphatidylinositol kinase activity with polyoma middle-T competent for transformation

@article{Whitman1985AssociationOP,
  title={Association of phosphatidylinositol kinase activity with polyoma middle-T competent for transformation},
  author={Malcolm Whitman and David R Kaplan and Brian S. Schaffhausen and Lewis C. Cantley and Thomas M. Roberts},
  journal={Nature},
  year={1985},
  volume={315},
  pages={239-242}
}
Polyoma middle-T antigen is required for viral transformation of cultured cells and for tumorigenesis in animals. Like many other transforming gene products, middle-T is bound to the membrane and has an associated tyrosine kinase activity in vitro1,2. This activity seems to result from the interaction of middle-T with pp60c-src, the cellular homologue of the transforming gene product of the Rous sarcoma virus, pp60v-src (refs 3–5). Both pp60v-src (ref. 6) and another retrovirus transforming… Expand
Membrane association of polyomavirus middle-T antigen in an in vitro system.
TLDR
It is shown in an in vitro system that middle-T fusion proteins carrying an amino-terminal hemagglutinin leader sequence are capable to bind to and enter the lumen of dog pancreas microsomes supporting the concept that the carboxy-terminus ofmiddle-T is an authentic membrane-targeting domain. Expand
The p110α Isoform of Phosphatidylinositol 3-Kinase Is Essential for Polyomavirus Middle T Antigen-Mediated Transformation
TLDR
A cross-species and cross-cell-type comparison of MT-induced transformation in cells with genetically defined backgrounds finds that the Y315F mutation disabled the ability of MT to induce transformation in all cell types and species tested, suggesting the mechanism by which MT activates the PI3K pathway differs in different species. Expand
Oncogenes and Phosphatidylinositol Turnover a
Products of phosphatidylinositol turnover have recently been implicated as regulators of cell growth and differentiation. Transformation of cells in culture by infection with certain viruses (RousExpand
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It is reported that MTAg is transiently modified during mitosis, resulting in an increase in its apparent molecular size on SDS/acrylamide gels, and data suggest that phosphorylation by p34cdc2 or a related cell cycle-regulated kinase modulates the interaction of MTAg with cellular targets that are crucial for cell transformation. Expand
Mutants of polyomavirus middle-T antigen.
TLDR
A model of middle-T is presented in which the protein is considered as consisting of three domains: a hydrophobic domain, the amino-terminal half of the molecule and the intervening amino acids (the putative modulatory domain). Expand
Polyomavirus middle-T antigen lacking a membrane anchor sequence accumulates in the nucleus.
TLDR
Three proteins expressed early in the replicative cycle of polyomavirus also play an essential role during virus-mediated tumorigenesis, and suggests that nuclear localization of truncated middle-T may be a consequence of binding to phosphatase 2A. Expand
Signaling from Polyomavirus Middle T and Small T Defines Different Roles for Protein Phosphatase 2A
TLDR
A functional difference in MT and ST signaling via PP2A is revealed, and transformation-defective mutants lacking association with SHC or with phosphatidylinositol 3-kinase retained the ability to induce DNA synthesis as measured by bromodeoxyuridine incorporation. Expand
Transformation-defective mutants of polyomavirus middle T antigen associate with phosphatidylinositol 3-kinase (PI 3-kinase) but are unable to maintain wild-type levels of PI 3-kinase products in intact cells
TLDR
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Polyoma virus middle t-antigen: growth factor receptor mimic
TLDR
Polyoma virus's middle T-antigen, MT, not only supplies information about the mechanisms behind tumor induction in vivo and transformation in cell culture, but can also be used to examine the molecular details of signal transduction induced by growth factor receptors. Expand
Lessons from polyoma middle T antigen on signaling and transformation: A DNA tumor virus contribution to the war on cancer.
Middle T antigen (MT) is the principal oncogene of murine polyomavirus. Its study has led to the discovery of the roles of tyrosine kinase and phosphoinositide 3-kinase (PI3K) signaling in mammalianExpand
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References

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Polyoma virus transforming protein associates with the product of the c-src cellular gene
TLDR
It is proposed that the middle T associated kinase at least in part is a property of pp60c-src rather than middle T itself, which is an intrinsic activity of the protein itself or the property of an associated enzyme. Expand
Transforming activity of polyoma virus middle-T antigen probed by site-directed mutagenesis
TLDR
Contrary to expectation, the results obtained strongly suggest that Tyr 315 and conservation of the surrounding amino acid sequence are not essential for transformation. Expand
Transforming protein of avian sarcoma virus UR2 is associated with phosphatidylinositol kinase activity: possible role in tumorigenesis.
TLDR
A mechanism whereby certain oncogene proteins might cause the unrestricted growth typical of transformed cells and could explain why tumor promoters mimic many of the effects of transformation is suggested. Expand
Enhancement of cellular src gene product associated tyrosyl kinase activity following polyoma virus infection and transformation
We examine the interaction between polyoma-virus-encoded middle tumor antigen and the cellular src gene product, pp60c-src, using a series of monoclonal antibodies that recognize mammalian pp60c-src.Expand
Carboxy terminus of polyoma middle-sized tumor antigen is required for attachment to membranes, associated protein kinase activities, and cell transformation.
TLDR
A transformation-defective polyoma virus mutant (Py 1387-T) is constructed that directs the synthesis of a normal small tumors antigen, a functional large tumor antigen, and a truncated middle-sized tumor (mT) antigen that lacks 37 amino acids at its COOH terminus. Expand
Evidence that the phosphorylation of tyrosine is essential for cellular transformation by Rous sarcoma virus
TLDR
Increased phosphorylation of tyrosine is neither a universal mechanism of transformation nor an inevitable secondary cellular response to transformation, suggesting strongly that the modification of one or more cellular polypeptides by way of pp60 src is critical for cellular transformation by Rous sarcoma virus. Expand
Evidence that the Rous sarcoma virus transforming gene product phosphorylates phosphatidylinositol and diacylglycerol.
TLDR
When serum-starved chicken embryo fibroblasts transformed by a virus mutant temperature-sensitive for transformation were shifted from the nonpermissive to permissive temperature, an increase of 50-100% in the labeling of phosphatidylinositol 4-phosphate, phosphatide 4,5-bisph phosphate, and phosph atidic acid was observed, as compared to uninfected cells. Expand
Transformation by polyoma virus is drastically reduced by substitution of phenylalanine for tyrosine at residue 315 of middle-sized tumor antigen.
TLDR
Reconstituted polyoma virus with the transversion of A----T transversion, Py-1178-T, produces an altered mT protein that shows about 20% of the activity of wild-type mT antigen in the immunocomplex kinase assay. Expand
The complex of polyoma virus middle‐T antigen and pp60c‐src.
TLDR
It is proposed that the complex plays an essential role in transformation by polyoma virus, but that the existence of the complex per se may not be sufficient. Expand
Monoclonal antibodies to Rous sarcoma virus pp60src react with enzymatically active cellular pp60src of avian and mammalian origin
TLDR
Mapping experiments have tentatively localized the determinant(s) recognized by GD11 and EB8 to a region of the src protein bounded by amino acid residues 82 to 169, whereas the remaining Mabs appeared to recognize determinants residing within residues 1 to 82 or 169 to 173. Expand
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