Regulation of Bcr-Abl-induced SAP kinase activity and transformation by the SHPTP1 protein tyrosine phosphatase.
The oncogenic Bcr-Abl variant of the c-Abl tyrosine kinase transforms cells by a mechanism dependent on activation of the stress-activated protein kinase (SAPK). Other work has shown that c-Abl interacts with the SHPTP1 protein tyrosine phosphatase in induction of SAPK activity by genotoxic stress. The present studies demonstrate that Bcr-Abl ... binds constitutively to SHPTP1. We show that Bcr-Abl phosphorylates SHPTP1 on C-terminal Y536 and Y564 sites. The functional significance of the Bcr-Abl/SHPTP1 interaction is supported by the finding that SHPTP1 regulates Bcr-Abl-induced SAPK activity. Importantly, SHPTP1 also decreases Bcr-Abl-dependent transformation of fibroblasts. These findings indicate that SHPTP1 functions as a tumor suppressor in cells transformed by Bcr-Abl.
Mesh Terms:
3T3 Cells, Animals, Calcium-Calmodulin-Dependent Protein Kinases, Cell Line, Transformed, Cell Transformation, Neoplastic, Down-Regulation, Enzyme Induction, Fusion Proteins, bcr-abl, Intracellular Signaling Peptides and Proteins, JNK Mitogen-Activated Protein Kinases, Mice, Mitogen-Activated Protein Kinases, Phosphorylation, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Protein Tyrosine Phosphatases
3T3 Cells, Animals, Calcium-Calmodulin-Dependent Protein Kinases, Cell Line, Transformed, Cell Transformation, Neoplastic, Down-Regulation, Enzyme Induction, Fusion Proteins, bcr-abl, Intracellular Signaling Peptides and Proteins, JNK Mitogen-Activated Protein Kinases, Mice, Mitogen-Activated Protein Kinases, Phosphorylation, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Protein Tyrosine Phosphatases
Oncogene
Date: Oct. 15, 1998
PubMed ID: 9788431
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