HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 276, Issue 21, 18130-18138, May 25, 2001

This Article Full Text Full Text (PDF) All Versions of this Article: 276/21/18130    most recent M007294200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ito, Y. Articles by Kharbanda, S. Search for Related Content PubMed PubMed Citation Articles by Ito, Y. Articles by Kharbanda, S. Social Bookmarking                      What's this?

Interaction of Hematopoietic Progenitor Kinase 1 and c-Abl Tyrosine Kinase in Response to Genotoxic Stress^*

Yasumasa Ito, Pramod Pandey, Pradeep Sathyanarayana^§, Pin Ling^¶, Ajay Rana^§, Ralph Weichselbaum, Tse-Hua Tan^¶, Donald Kufe, and Surender Kharbanda^**

From the  Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, ^§ Diabetes Research Laboratory, Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114,  Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois 60637, and ^¶ Department of Immunology, Baylor College of Medicine, Houston, Texas 77030

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.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				G. Zhou, J. S. Boomer, and T.-H. Tan Protein Phosphatase 4 Is a Positive Regulator of Hematopoietic Progenitor Kinase 1 J. Biol. Chem., November 19, 2004; 279(47): 49551 - 49561. [Abstract] [Full Text] [PDF]

				P. Ling, C. F. Meyer, L. P. Redmond, J.-W. Shui, B. Davis, R. R. Rich, M. C.-T. Hu, R. L. Wange, and T.-H. Tan Involvement of Hematopoietic Progenitor Kinase 1 in T Cell Receptor Signaling J. Biol. Chem., May 25, 2001; 276(22): 18908 - 18914. [Abstract] [Full Text] [PDF]