Association of Polyomavirus Middle Tumor Antigen with 14-3-3 Proteins

Pallas, David C.; Fu, Haian; Haehnel, L. C.; Weller, W.; Collier, R. J.; Roberts, Thomas M.

doi:10.1126/science.8036498

Cited by 158 publications

(85 citation statements)

References 13 publications

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“…A novel type of protein kinase inhibitor (KCIP) originally isolated from sheep brain [24] belongs to this family as well as neuronal protein kinase-dependent activators of tyrosine or tryptophan hydroxylases involved in monoamine neurotransmitter biosynthesis [25]. 14-3-3 proteins are further involved in the regulation of calcium-dependent exocytosis in animal cells [23], the timing of mitosis in Schizosucchuromyces pombe [26] and the development of neoplasia [27]. In plants, 143-3 homologs have been described in several species and various contexts.…”

Section: Discussionmentioning

confidence: 99%

The fusicoccin receptor of plants is a member of the 14‐3‐3 superfamily of eukaryotic regulatory proteins

1994

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The receptor for the wilt-inducing phytotoxin fusicoccin was purified to homogeneity from plasma membranes of Commelina communis as a complex with the radioligand [3H]9'-nor-8'-hydroxyfusicoccin. The preparation consisted of two polypeptides with apparent molecular masses of 30.5 kDa and 31.5 kDa and with isoelectric points of around pH 5.2 and 5.3, respectively. The proteins were N-terminally blocked. Internal amino acid sequences were obtained for both polypeptides of the fusicoccin-binding complex. Sequence information, as well as subsequent immunological analysis, proved that both polypeptides are members of the eukaryotic 143-3 family, which comprises structurally conserved regulatory proteins of widespread occurrence and a wide range of functions. 143-3 isoform(s) constituting the fusicoccin receptor are distinguishable from other cellular 143-3 proteins by their tight association with the plasma membrane. Applying temperature-induced Triton X-l 14 phase separation experiments, they, as well as the target enzyme of fusicoccin action, the H'-ATPase, partitioned into the phospholipid-rich fraction which contains the most hydrophobic proteins. The results discussed herein provide a basis for the elucidation of the molecular mechanism of fusicoccin action.

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Section: Discussionmentioning

confidence: 99%

The fusicoccin receptor of plants is a member of the 14‐3‐3 superfamily of eukaryotic regulatory proteins

1994

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“…Disruption of any of these interactions abrogates cell transformation by MT. In addition, phosphorylated Ser257 in MT interacts with members of the 14-3-3 family of proteins (Cullere et al, 1998;Pallas et al, 1994). This in¯uences the type of tumours induced in animals, but has little e ect on transformation of cells in culture.…”

Section: Introductionmentioning

confidence: 99%

Association between src-kinases and the polyoma virus oncogene middle T-antigen requires PP2A and a specific sequence motif

1999

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Polyoma virus encodes a potent oncogene, the middle Tantigen (MT), that induces cell transformation by copying the actions of tyrosine kinase associated growth factor receptors. A crucial component of MT transformation is its ability to bind and stimulate the activity of src-family kinases. However, the mechanism by which this is achieved remains unclear. Tyrosine phosphorylation of MT by src-kinases then provides binding sites for SH2 and PTB domain containing molecules in a paradigm of receptor action. We present evidence here that the MT/src complex contains equi-molar amounts of PP2A, and that phosphatase activity may be required for the interaction of MT with both PP2A and the srcfamily. PP2A, then, is a necessary component of the MT-src complex. We also show that two motifs in the 185 to 210 region of MT, each consisting of a basic area followed by a serine or threonine, are essential for interaction with src-kinases, but not PP2A. The spacing between the serine or threonine and the basic sequence also appears to be important. Substituting a cysteine residue in place of Thr203 in MT has no a ect on the binding of pp60 c-src , showing that these sites interact with src-kinases by a novel mechanism that does not require phosphorylation.

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“…Polyoma MT also binds the src family tyrosine kinases pp62c-es and pp62c-ftn, interacts with and stimulates the P13 kinase, PP2A, c-raf-1 and Shc (Courtneidge, 1994;Dilworth et al, 1994). Moreover, the Py-MT pathways activate phospholipase Cy and members of the 14-3-3 protein family (Pallas et al, 1994). Py-MT therefore mimics some of the intermolecular interactions and activation of signalling pathways controlled by activated growth factor receptors.…”

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confidence: 99%

Progression of familial adenomatous polyposis (FAP) colonic cells after transfer of the src or polyoma middle T oncogenes: cooperation between src and HGF/Met in invasion

et al. 1997

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Summary Little is known about the the signalling pathways driving the adenoma-to-carcinoma sequence in human colonic epithelial cells. Accumulation and activation of the src tyrosine kinase in colon cancer suggest a potential role of this oncogene in this early progression. Therefore, we introduced either activated src (m-src), polyoma-MT alone or combined with normal c-src in the adenoma PC/AA/C1 cell line (PC) to define the function and phenotypic transformations induced by these oncogenes in familial adenomatous polyposis (FAP) colonic epithelial cells. Functional expression of these oncoproteins induced the adenoma-to-carcinoma conversion, overexpression of the hepatocyte growth factor (HGF) receptor Met, but failed to confer invasiveness in vivo and in vitro, or to produce alterations in cell proliferation and differentiation. In contrast, PC-msrc cells became susceptible to the HGF-induced invasion of collagen gels and exhibited sustained activation of the pp6osrctyrosine kinase and Tyr phosphorylation of the 120-kDa E-cadherin, which was further increased by HGF Transcripts of HGF were clearly identified by reverse transcription -polymerase chain reaction (RT-PCR) and Southern blot in the parental and transformed PC cells, suggesting an autocrine mechanism. Taken together, the data indicate that: (1) experimental activation of src and PyMT pathways directly induces tumorigenicity and Met upregulation in a colon adenoma cell line; (2) HGF-activated Met and src cooperate in inducing invasion; (3) in view of the molecular associations between catenins and cadherin or the tumour-suppressor gene product APC, the cell adhesion molecule E-cadherin may constitute a downstream effector of src and Met.

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Association of Polyomavirus Middle Tumor Antigen with 14-3-3 Proteins

Cited by 158 publications

References 13 publications

The fusicoccin receptor of plants is a member of the 14‐3‐3 superfamily of eukaryotic regulatory proteins

The fusicoccin receptor of plants is a member of the 14‐3‐3 superfamily of eukaryotic regulatory proteins

Association between src-kinases and the polyoma virus oncogene middle T-antigen requires PP2A and a specific sequence motif

Progression of familial adenomatous polyposis (FAP) colonic cells after transfer of the src or polyoma middle T oncogenes: cooperation between src and HGF/Met in invasion

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