Sf-Stk kinase activity and the Grb2 binding site are required for Epo-independent growth of primary erythroblasts infected with Friend virus

Lisa D. Finkelstein, Paul A. Ney, Qing Ping Liu, Robert F. Paulson, Pamela H. Correll

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

During the initial stage of Friend virus-induced erythroleukemia in mice, interaction of the viral protein gp55 with the erythropoietin receptor, and other host factors, drives the expansion of erythroid precursor cells. Recently, we demonstrated that the Friend virus susceptibility locus, Fv2, which is required for the expansion of infected cells, encodes a naturally occurring, N-terminally truncated form of the Stk receptor tyrosine kinase (Sf-Stk). Here we show that in vitro expression of Sf-Stk confers Friend virus sensitivity to erythroid progenitor cells from Fv2rr mice. Furthermore, our data reveal that Sf-Stk kinase activity and Y436, but not Y429, are required for Epo-independent colony formation following Friend virus infection. Introduction of a mutation that results in failure to bind Grb2 abrogates the ability of Sf-Stk to induce colonies in response to Friend virus, while the Grb2 binding site from EGFR restores this response. Consistent with the ability of Grb2 to recruit SOS and Gabl, the Ras/MAPK and PI3K pathways are activated by Sf-Stk, and both of these pathways are required for gp55-mediated erythroblast proliferation. These data clearly demonstrate a requirement for signaling through Sf-Stk in the Epo-independent expansion of Friend virus-infected cells, and suggest a pivotal role for Grb2 in this response.

Original languageEnglish (US)
Pages (from-to)3562-3570
Number of pages9
JournalOncogene
Volume21
Issue number22
DOIs
StatePublished - Jan 1 2002

Fingerprint

Friend murine leukemia virus
Erythroblasts
Phosphotransferases
Binding Sites
Growth
Erythroid Precursor Cells
Erythropoietin Receptors
Leukemia, Erythroblastic, Acute
Receptor Protein-Tyrosine Kinases
Viral Proteins
Virus Diseases
Phosphatidylinositol 3-Kinases
Mutation

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Finkelstein, Lisa D. ; Ney, Paul A. ; Liu, Qing Ping ; Paulson, Robert F. ; Correll, Pamela H. / Sf-Stk kinase activity and the Grb2 binding site are required for Epo-independent growth of primary erythroblasts infected with Friend virus. In: Oncogene. 2002 ; Vol. 21, No. 22. pp. 3562-3570.
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Sf-Stk kinase activity and the Grb2 binding site are required for Epo-independent growth of primary erythroblasts infected with Friend virus. / Finkelstein, Lisa D.; Ney, Paul A.; Liu, Qing Ping; Paulson, Robert F.; Correll, Pamela H.

In: Oncogene, Vol. 21, No. 22, 01.01.2002, p. 3562-3570.

Research output: Contribution to journalArticle

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