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

Oncogene. 1995 Apr 6;10(7):1385-91.

Abstract

Expression of p210 BCR/abl oncoprotein transforms hematopoietic cells. P210 BCR/abl tyrosine kinase induces tyrosine phosphorylation of Shc, and activation of p21ras 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Adaptor Proteins, Vesicular Transport*
  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Fusion Proteins, bcr-abl / metabolism*
  • GRB2 Adaptor Protein
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism*
  • Mice
  • Molecular Sequence Data
  • Phosphatidylinositol 3-Kinases
  • Phosphorylation
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Phosphotyrosine
  • Protein Binding
  • Proteins / metabolism*
  • Shc Signaling Adaptor Proteins
  • Signal Transduction
  • Src Homology 2 Domain-Containing, Transforming Protein 1
  • Structure-Activity Relationship
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport
  • GRB2 Adaptor Protein
  • Grb2 protein, mouse
  • Proteins
  • Shc Signaling Adaptor Proteins
  • Shc1 protein, mouse
  • Src Homology 2 Domain-Containing, Transforming Protein 1
  • Phosphotyrosine
  • Tyrosine
  • Phosphatidylinositol 3-Kinases
  • Phosphotransferases (Alcohol Group Acceptor)
  • Fusion Proteins, bcr-abl