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

Duygu Dee Harrison-Findik, M. Susa, L. Varticovski

Research output: Contribution to journalArticle

64 Citations (Scopus)

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 - Jan 1 1995

Fingerprint

Phosphatidylinositol 3-Kinase
Leukemia
src Homology Domains
Phosphatidylinositol 3-Kinases
Oncogene Proteins
Tyrosine
Proto-Oncogene Proteins p21(ras)
Immunoprecipitation
Proline
Protein-Tyrosine Kinases
Phosphorylation

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

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

Association of phosphatidylinositol 3-kinase with SHC in chronic myelogeneous leukemia cells. / Harrison-Findik, Duygu Dee; Susa, M.; Varticovski, L.

In: Oncogene, Vol. 10, No. 7, 01.01.1995, p. 1385-1391.

Research output: Contribution to journalArticle

Harrison-Findik, DD, Susa, M & Varticovski, L 1995, 'Association of phosphatidylinositol 3-kinase with SHC in chronic myelogeneous leukemia cells', Oncogene, vol. 10, no. 7, pp. 1385-1391.
Harrison-Findik DD, Susa M, Varticovski L. Association of phosphatidylinositol 3-kinase with SHC in chronic myelogeneous leukemia cells. Oncogene. 1995 Jan 1;10(7):1385-1391.
Harrison-Findik, Duygu Dee ; Susa, M. ; Varticovski, L. / Association of phosphatidylinositol 3-kinase with SHC in chronic myelogeneous leukemia cells. In: Oncogene. 1995 ; Vol. 10, No. 7. pp. 1385-1391.
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