A novel Stat3 binding motif in Gab2 mediates transformation of primary hematopoietic cells by the Stk/Ron receptor tyrosine kinase in response to friend virus infection

Shuang Ni, Chunmei Zhao, Gen Sheng Feng, Robert F. Paulson, Pamela H. Correll

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Friend erythroleukemia vims has long served as a paradigm for the study of the multistage progression of leukemia. Friend virus infects erythroid progenitor cells, followed by an initial polyclonal expansion of infected cells, which is driven by the activation of a naturally occurring truncated form of the Stk receptor tyrosine kinase (Sf-Stk). Subsequently, the accumulation of additional mutations in p53 and the activation of PU.1 result in full leukemic transformation. The early stages of transformation induced by Friend virus are characterized in vitro by the Epo-independent growth of infected erythroblasts. We have shown previously that this transforming event requires the kinase activity and Grb2 binding site of Sf-Stk and the recruitment of a Grb2/Gab2 complex to Sf-Stk. Here, we demonstrate that Stat3 is required for the Epo-independent growth of Friend virus-infected cells and that the activation of Stat3 by Sf-Stk is mediated by a novel Stat3 binding site in Gab2. These results underscore a central role for Stat3 in hematopoietic transformation and describe a previously unidentified role for Gab2 in the recruitment and activation of Stat3 in response to transforming signals generated by tyrosine kinases.

Original languageEnglish (US)
Pages (from-to)3708-3715
Number of pages8
JournalMolecular and cellular biology
Volume27
Issue number10
DOIs
StatePublished - May 1 2007

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Friend murine leukemia virus
Receptor Protein-Tyrosine Kinases
Virus Diseases
Binding Sites
Erythroblasts
Leukemia, Erythroblastic, Acute
Erythroid Precursor Cells
Growth
Protein-Tyrosine Kinases
Leukemia
Phosphotransferases

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

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title = "A novel Stat3 binding motif in Gab2 mediates transformation of primary hematopoietic cells by the Stk/Ron receptor tyrosine kinase in response to friend virus infection",
abstract = "Friend erythroleukemia vims has long served as a paradigm for the study of the multistage progression of leukemia. Friend virus infects erythroid progenitor cells, followed by an initial polyclonal expansion of infected cells, which is driven by the activation of a naturally occurring truncated form of the Stk receptor tyrosine kinase (Sf-Stk). Subsequently, the accumulation of additional mutations in p53 and the activation of PU.1 result in full leukemic transformation. The early stages of transformation induced by Friend virus are characterized in vitro by the Epo-independent growth of infected erythroblasts. We have shown previously that this transforming event requires the kinase activity and Grb2 binding site of Sf-Stk and the recruitment of a Grb2/Gab2 complex to Sf-Stk. Here, we demonstrate that Stat3 is required for the Epo-independent growth of Friend virus-infected cells and that the activation of Stat3 by Sf-Stk is mediated by a novel Stat3 binding site in Gab2. These results underscore a central role for Stat3 in hematopoietic transformation and describe a previously unidentified role for Gab2 in the recruitment and activation of Stat3 in response to transforming signals generated by tyrosine kinases.",
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A novel Stat3 binding motif in Gab2 mediates transformation of primary hematopoietic cells by the Stk/Ron receptor tyrosine kinase in response to friend virus infection. / Ni, Shuang; Zhao, Chunmei; Feng, Gen Sheng; Paulson, Robert F.; Correll, Pamela H.

In: Molecular and cellular biology, Vol. 27, No. 10, 01.05.2007, p. 3708-3715.

Research output: Contribution to journalArticle

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AU - Correll, Pamela H.

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