Association of phosphatidylinositol 3-kinase with SHC in chronic myelogeneous leukemia cells

D. Harrison-Findik, M. Susa, L. Varticovski

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

Expression of p210 BCR/abl oncoprotein transforms hematopoietic cells. P210 BCR/abl tyrosine kinase induces tyrosine phosphorylation of Shc, and activation of p21(ras) and PI 3-Kinase. Here we show that PI 3-Kinase associates with Shc in cells transformed by BCR/abl oncoprotein. Immunoprecipitation of Shc from cells expressing p210 BCR/abl had 7.5-fold increase in PI 3-Kinase activity compared to parental cells. Tyrosine phosphorylated Shc specifically bound to the C-SH2 domain of the p85 subunit of PI 3-Kinase. The p85 SH3 domain also interacted with Shc in cell lysates from parental and transformed cells. The binding of p85 SH3 domain to Shc was substantially higher in BCR/abl transformed than in parental cells. Phenylphosphate blocked p85 SH2 mediated association with Shc but enhanced the binding of the p85 SH3 domain to Shc. The N-terminal proline-rich region of Shc between A263 and N273 specifically blocked the interaction of p85 SH3 domain with Shc. Our results indicate that PI 3-Kinase interacts with Shc directly in hematopoietic cells which express p210 BCR/abl oncoprotein.

Original languageEnglish (US)
Pages (from-to)1385-1391
Number of pages7
JournalOncogene
Volume10
Issue number7
StatePublished - 1995

Keywords

  • BCR/abl
  • PI 3-kinase
  • SH2
  • SH3
  • Shc
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Harrison-Findik, D., Susa, M., & Varticovski, L. (1995). Association of phosphatidylinositol 3-kinase with SHC in chronic myelogeneous leukemia cells. Oncogene, 10(7), 1385-1391.