Interaction of hematopoietic progenitor kinase 1 and c-Abl tyrosine kinase in response to genotoxic stress

J Biol Chem. 2001 May 25;276(21):18130-8. doi: 10.1074/jbc.M007294200. Epub 2001 Jan 30.


The c-Abl protein tyrosine kinase is activated by certain DNA-damaging agents and regulates induction of the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK). The hematopoietic progenitor kinase 1 (HPK1) has also been shown to act upstream to the SAPK/JNK signaling pathway. We report here that exposure of hematopoietic Jurkat T cells to genotoxic agents is associated with activation of HPK1. The results demonstrate that exposure of Jurkat cells to DNA-damaging agents is associated with translocation of active c-Abl from nuclei to cytoplasm and binding of c-Abl to HPK1. Our findings also demonstrate that c-Abl phosphorylates HPK1 in cytoplasm and stimulates HPK1 activity. The functional significance of the c-Abl-HPK1 interaction is supported by the demonstration that this complex regulates SAPK/JNK activation. Overexpression of c-Abl(K-R) inhibits HPK1-induced activation of SAPK/JNK. Conversely, the dominant negative mutant of HPK1 blocks c-Abl-mediated induction of SAPK/JNK. These findings indicate that activation of HPK1 and formation of HPK1/c-Abl complexes are functionally important in the stress response of hematopoietic cells to genotoxic agents.

Publication types

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

MeSH terms

  • Enzyme Activation
  • Humans
  • Jurkat Cells
  • MAP Kinase Signaling System
  • Protein Serine-Threonine Kinases / physiology*
  • Proto-Oncogene Proteins c-abl / physiology*
  • Signal Transduction / radiation effects*
  • T-Lymphocytes / physiology*
  • T-Lymphocytes / radiation effects*


  • hematopoietic progenitor kinase 1
  • Proto-Oncogene Proteins c-abl
  • Protein Serine-Threonine Kinases