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

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.
Mesh Terms:
1-Phosphatidylinositol 3-Kinase, Adaptor Proteins, Signal Transducing, Adaptor Proteins, Vesicular Transport, Amino Acid Sequence, Animals, Cell Line, Fusion Proteins, bcr-abl, GRB2 Adaptor Protein, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Mice, Molecular Sequence Data, Phosphorylation, Phosphotransferases (Alcohol Group Acceptor), Phosphotyrosine, Protein Binding, Proteins, Shc Signaling Adaptor Proteins, Signal Transduction, Structure-Activity Relationship, Tyrosine
Oncogene
Date: Apr. 06, 1995
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