Friend spleen focus-forming virus transforms rodent fibroblasts in cooperation with a short form of the receptor tyrosine kinase Stk

Nishigaki, Kazuo; Hanson, Charlotte; Jelacic, Tanya; Thompson, Delores; Ruscetti, Sandra K.

doi:10.1073/pnas.0506570102

Cited by 21 publications

(35 citation statements)

References 26 publications

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“…21 Furthermore, our previous data indicated that a deletion mutant in which the N-terminal extracellular domain (55 aa) of sf-Stk was deleted was unable to transform SFFV-P-and SFFV-A-infected NIH3T3 cells. 23 Therefore, the extracellular sequences of sf-Stk are crucial for efficient transformation of fibroblasts by SFFV. In this study, we constructed 10 continuous deletion mutants within a 55 amino acid stretch of the sf-Stk N-terminal extracellular domain (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…293T cells, NIH3T3 cells, SFFV-P/NIH3T3 and SFFV-A/ NIH3T3 23 (transfected with SFFV-P and SFFV-A, respectively) were cultured in Dulbecco's minimal essential medium supplemented with 10% fetal calf serum.…”

Section: Cellsmentioning

confidence: 99%

“…Wild-type sf-Stk 23 and the sf-Stk mutants with a myc tag at the C-terminus of sf-Stk were cloned into the pEF6 expression vector (Invitrogen) via the EcoRI and BamHI sites. The following sf-Stk deletion constructs and point mutants were generated by polymerase chain reaction (PCR) using pEFsf-Stk (wild-type) as a template and the following forward primers:…”

Section: Plasmidsmentioning

confidence: 99%

“…21 Furthermore, Env gp55 from SFFV-P and SFFV-A transform rodent fibroblasts in cooperation with sf-Stk through activation of sf-Stk without EpoR signaling. 23 The direct activation of sf-Stk by SFFV Env most likely also occurs in SFFV-infected erythroid cells and induces, at least, erythroid proliferation. 9,24 The interaction between SFFV gp55 and sf-Stk was detected by the formation of both disulfide-linked and non-disulfide-linked complexes.…”

mentioning

confidence: 99%

“…9,24 The interaction between SFFV gp55 and sf-Stk was detected by the formation of both disulfide-linked and non-disulfide-linked complexes. 21,23 Therefore, in this study, we attempted to determine the critical amino acid sequences within sf-Stk that are necessary for SFFV Env gp55 binding and induction of fibroblast formation in cooperation with SFFV. Our results indicate that the fibroblast transformation patterns induced by sfStk/SFFV gp55 complex formation are different for SFFV-P and SFFV-A.…”

mentioning

confidence: 99%

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Role of N‐terminal sequences of the tyrosine kinase sf‐Stk in transformation of rodent fibroblasts by variants of Friend spleen focus‐forming virus

Umehara

Kawamura

Odahara

et al. 2011

Intl Journal of Cancer

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Infection of erythroid cells by Friend spleen focus-forming virus (SFFV) leads to acute erythroid hyperplasia in mice, due to expression of its unique envelope glycoprotein, gp55. Erythroid cells expressing SFFV gp55 proliferate in the absence of their normal regulator, erythropoietin, because of the interaction among the viral envelope protein, the erythropoietin receptor, and a short form of the receptor tyrosine kinase Stk (sf-Stk). This leads to constitutive activation of several signal transduction pathways. Our previous studies showed that sf-Stk interacts with SFFV gp55, forming disulfide-linked complexes. This covalent interaction, along with other noncovalent interactions with SFFV-gp55, results in constitutive tyrosine phosphorylation of sf-Stk and rodent fibroblast transformation. Here, we determined the precise amino acid region within sf-Stk that contributes to fibroblast transformation by the polycythemia-inducing (SFFV-P) and the anemia-inducing (SFFV-A) strains of SFFV. Sf-Stk deletion mutants showed different transforming abilities in fibroblasts infected with SFFV-P and SFFV-A, although the N-terminal extracellular domain of sf-Stk was essential for fibroblast transformation by both viruses. Point mutations of sf-Stk indicated that cysteine 19 was critical for fibroblast transformation by SFFV-P, although all four cysteines (8, 19, 37 and 42) appeared to be important for fibroblast transformation by both SFFV-P and SFFV-A. Mutation of sf-Stk cysteine 19 abolished its ability to form dimers with SFFV-P and SFFV-A gp55. These results suggest that the interaction between sf-Stk and the envelope proteins of the polycythemia-and anemia-inducing variants of SFFV is architecturally different.The Friend spleen focus-forming virus (SFFV) is a highly pathogenic retrovirus that induces rapid erythroblastosis in susceptible strains of mice.1 Friend SFFV is a replication-defective virus with deletions in its env gene that give rise to a unique glycoprotein, SFFV gp55. This unique glycoprotein confers pathogenicity on the virus; a vector encoding SFFV gp55 alone is sufficient to induce erythroblastosis in susceptible strains of mice.2 The Fv-2 gene encodes one of the key susceptibility factors for SFFV-induced erythroid disease 3,4 : the receptor tyrosine kinase Stk/RON, a member of the Met family of receptor tyrosine kinases. 5,6 Susceptibility to SFFVinduced disease is associated with expression of a short form of Stk, termed sf-Stk, which is transcribed from an internal promoter within the Stk gene of susceptible mice (Fv-2 ss ) but not in resistant mice (Fv-2 rr ), 4 and is abundantly expressed in erythroid cells.5 Infection of Fv-2 ss erythroid cells with the polycythemia-inducing strain of SFFV (SFFV-P) induces erythropoietin (Epo)-independent proliferation and differentiation, whereas erythroid cells infected with the anemiainducing strain of SFFV (SFFV-A) proliferate in the absence of Epo but still require Epo for differentiation.7 A number of signaling pathways, normally activated in erythroid cells...

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Section: Resultsmentioning

confidence: 99%

Section: Cellsmentioning

confidence: 99%

Section: Plasmidsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Role of N‐terminal sequences of the tyrosine kinase sf‐Stk in transformation of rodent fibroblasts by variants of Friend spleen focus‐forming virus

Umehara

Kawamura

Odahara

et al. 2011

Intl Journal of Cancer

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Oncogenesis by retroviruses: old and new paradigms

Maeda

Fan

Yoshikai

2008

Reviews in Medical Virology

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Retroviruses are associated with a variety of diseases including an array of malignancies, immunodeficiencies and neurological disorders. In particular, studies of oncogenic retroviruses established fundamental principles of modern molecular cancer biology. Studies of avian Rous sarcoma virus (RSV) led to the discovery of the viral oncogene src, and this was followed by the discovery of other viral oncogenes in retroviruses of mammals including rodents, cats, monkeys and so forth. Studies of the viral oncogenes in turn led to the discovery of cellular proto-oncogenes in the host genome; cellular oncogenes have been shown to be activated in a variety of human cancers, including those with no viral involvement. Oncogenic animal retroviruses can be divided into two groups based on their mechanisms of tumourigenesis, acute transforming retroviruses and nonacute retroviruses. Acute transforming retroviruses are typically replication defective and they induce tumours rapidly due to expression of their viral oncogenes. Nonacute retroviruses are replication competent and they induce tumours with longer latencies, by activating cellular proto-oncogenes in the tumour cells; this results from insertion of proviral DNA in the vicinity of the activated proto-oncogene. More recently, human T-cell leukaemia virus type I (HTLV-I) was discovered as an etiological agent of human cancer (adult T-cell leukaemia [ATL]); this virus also encodes regulatory genes some of which are important for its oncogenic potential. Most recently, the retroviral structural protein Envelope (Env) has been shown to be directly involved in oncogenic transformation for certain retroviruses. Env-induced transformation is a new paradigm for retroviral oncogenesis. In this review, we will summarise research on retrovirus oncogenic transformation over the past 100 years since the first published report of an oncogenic virus with particular attention to Env-induced transformation.

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Deregulation of Signal Transduction Pathways by Oncogenic Retroviruses

Ruscetti

Cmarik²

2010

Retroviruses and Insights Into Cancer

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Friend spleen focus-forming virus transforms rodent fibroblasts in cooperation with a short form of the receptor tyrosine kinase Stk

Cited by 21 publications

References 26 publications

Role of N‐terminal sequences of the tyrosine kinase sf‐Stk in transformation of rodent fibroblasts by variants of Friend spleen focus‐forming virus

Role of N‐terminal sequences of the tyrosine kinase sf‐Stk in transformation of rodent fibroblasts by variants of Friend spleen focus‐forming virus

Oncogenesis by retroviruses: old and new paradigms

Deregulation of Signal Transduction Pathways by Oncogenic Retroviruses

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