Regulation of the Src Homology 2-containing Inositol 5-Phosphatase SHIP1 in HIP1/PDGFβR-transformed Cells

Djenann Saint-Dic, Samantha C. Chang, Gregory S. Taylor, Melissa M. Provot, Theodora S. Ross

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

It has been shown previously that the Huntingtin interacting protein 1 gene (HIP1) was fused to the platelet-derived growth factor β receptor gene (PDGFβR) in leukemic cells of a patient with chronic myelomonocytic leukemia. This resulted in the expression of the chimeric HIP1/PDGFβR protein, which oligomerizes, is constitutively tyrosine-phosphorylated, and transforms the Ba/F3 murine hematopoietic cell line to interleukin-3-independent growth. Tyrosine phosphorylation of a 130-kDa protein (p130) correlates with transformation by HIP1/PDGFβR and related transforming mutants. We report here that the p130 band is immunologically related to the 125-kDa isoform of the Src homology 2-containing inositol 5-phosphatase, SHIP1. We have found that SHIP1 associates and colocalizes with the HIP1/PDGFβR fusion protein and related transforming mutants. These mutants include a mutant that has eight Src homology 2-binding phosphotyrosines mutated to phenylalanine. In contrast, SHIP1 does not associate with H/P(KI), the kinase-dead form of HIP1/PDGFβR. We also report that phosphorylation of SHIP1 by HIP1/PDGFβR does not change its 5-phosphatase-specific activity. This suggests that phosphorylation and possible PDGFβR-mediated sequestration of SHIP1 from its substrates (PtdIns(3,4,5)P3 and Ins(1,3,4,5)P4) might alter the levels of these inositol-containing signal transduction molecules, resulting in activation of downstream effectors of cellular proliferation and/or survival.

Original languageEnglish (US)
Pages (from-to)21192-21198
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number24
DOIs
StatePublished - Jun 15 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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