Transforming properties of the huntingtin interacting protein 1/platelet-derived growth factor β receptor fusion protein

Theodora S. Ross, D. Gary Gilliland

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

We have previously reported that the Huntingtin interacting protein 1 (HIP1) gene is fused to the platelet-derived growth factor β receptor (PDGFβR) gene in a patient with chronic myelomonocytic leukemia. We now show that HIP1/PDGFβR oligomerizes, is constitutively tyrosine-phosphorylated, and transforms the murine hematopoietic cell line, Ba/F3, to interleukin-3- independent growth. A kinase-inactive mutant is neither tyrosine- phosphorylated nor able to transform Ba/F3 cells. Oligomerization and kinase activation required the 55-amino acid carboxyl-terminal TALIN homology region but not the leucine zipper domain. Tyrosine phosphorylation of a 130-kDa protein and STAT5 correlates with transformation in cells expressing HIP1/PDGFβR and related mutants. A deletion mutant fusion protein that contains only the TALIN homology region of HIP1 fused to PDGFβR is incapable of transforming Ba/F3 cells and does not tyrosine-phosphorylate p130 or STAT5, although it is itself constitutively tyrosine-phosphorylated. We have also analyzed cells expressing Tyr → Phe mutants of HIP1/PDGFβR in the known PDGFβR SH2 docking sites and report that none of these sites are necessary for STAT5 activation, p130 phosphorylation, or Ba/F3 transformation. The correlation of factor-independent growth of hematopoietic cells with p130 and STAT5 phosphorylation/activation in both the HIP1/PDGFβR Tyr → Phe and deletion mutational variants suggests that both STAT5 and p130 are important for transformation mediated by HIP1/PDGFβR.

Original languageEnglish (US)
Pages (from-to)22328-22336
Number of pages9
JournalJournal of Biological Chemistry
Volume274
Issue number32
DOIs
StatePublished - Aug 6 1999

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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