Identification and characterization of the hamster polyomavirus middle T antigen

Abstract

Hamster polyomavirus (HaPV) is associated with lymphoid and hair follicle tumors in Syrian hamsters. The early region of HaPV has the potential to encode three polypeptides (which are related to the mouse polyomavirus early proteins) and can transform fibroblasts in vitro. We identified the HaPV middle T antigen (HamT) as a 45-kDa protein. Like its murine counterpart, HamT was associated with serine/threonine phosphatase, phosphatidylinositol-3 kinase, and protein tyrosine kinase activities. However, whereas mouse middle T antigen associates predominantly with pp60c-src and pp62c-yes, HamT was associated with a different tyrosine kinase, p59fyn. The ability of HaPV to cause lymphoid tumors may therefore reside in its ability to associate with p59fyn, a potentially important tyrosine kinase in lymphocytes.

Trichodysplasia Spinulosa-A Rare Complication in Immunosuppressed Patients

“…BK virus, which is a polyomavirus, can be detected frequently in the urinary tract of kidney and bone marrow recipients (12). Also, hair follicle tumors similar to the lesions described here were shown to be associated with a polyomavirus in mice and hamsters (13), and immunocompromised patients are known to be predisposed to infections with the human papillomavirus (14). Finally, the fact that two patients showed good improvement with 3% topical cidofovir (5,10), an antiviral medication that has been shown to be somewhat successful in treating BK virus associated nephropathy when administered intravenously (15), would also support the theory of a virus-induced pathology.…”

Phosphorylation sites in the PDGF receptor with different specificities for binding GAP and PI3 kinase in vivo.

“…Two different PDGF receptor polypeptides, the ox-and (-subunits, differ in their specificity for different isoforms of PDGF (reviewed in Heldin and Westermark, 1990). The (-receptor binds P13 kinase, PLC'y, GAP, Src, Fyn, Yes, tensin and Raf (which lacks an SH2 domain) (Kaplan et al, 1987;Kumjian et al, 1989; Morrison et al, 1990;Kaplan et al, 1990;Kypta et al, 1990;Courtneidge et al, 1991;Davis et al, 1991;Morrison et al, 1989). Site-directed mutagenesis has been used to define the features of the PDGF (-receptor required for binding.…”

Functional interaction between the SH2 domain of Fyn and tyrosine 324 of hamster polyomavirus middle-T antigen

“…While large-T antigen is able to immortalize primary rodent fibroblasts, both middle-T and large-T antigens are necessary for induction of a fully transformed phenotype and small-T antigen potentiates the efficiency of transformation (reviewed in reference 10). Middle-T antigen of mouse polyomavirus (MomT) is sufficient for transformation of established cells (45), while middle-T antigen of hamster polyomavirus (HamT) (8) was shown to transform established F111 rat cells only in the presence of small-T antigen (16).…”

“…The middle-T proteins of mouse and hamster polyomaviruses have an overall sequence identity of 41% (8). Regions of higher homology are clustered along the sequence.…”

“…Middle-T proteins of both polyomaviruses have been shown to associate with and thereby change the activities of several cellular proteins that play a key role in the growth regulation of cells, including phosphatase 2A (8,31,47), Src-related tyrosine kinases (reviewed in reference 12), PI 3-kinase (8,48), phospholipase C-␥1 (2,42), and 14-3-3 proteins (30). MomT was also shown to bind the adapter protein SHC (3,13), thus activating the Ras pathway (46).…”