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Research ArticleArticle

Negative Regulation of the SHPTP1 Protein Tyrosine Phosphatase by Protein Kinase C δ in Response to DNA Damage

Kiyotsugu Yoshida and Donald Kufe
Molecular Pharmacology December 2001, 60 (6) 1431-1438; DOI: https://doi.org/10.1124/mol.60.6.1431
Kiyotsugu Yoshida
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts
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Donald Kufe
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts
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Abstract

The SHPTP1 protein tyrosine phosphatase is activated by the c-Abl and Lyn tyrosine kinases in the cellular response to genotoxic stress. However, signaling mechanisms involved in the negative regulation of SHPTP1 are unknown. This study demonstrates that protein kinase C δ (PKCδ) associates with SHPTP1. The PKCδ catalytic domain binds directly to SHPTP1. The results also demonstrate that PKCδ is required, at least in part, for phosphorylation and inactivation of SHPTP1. The phosphatase activity of SHPTP1 was attenuated by coincubation with PKCδ in vitro. In addition, treatment of U-937 human myeloid leukemia cells with 1-β-d-arabinofuranosylcytosine (ara-C) was associated with induction of the PKCδ kinase function and inhibition of SHPTP1 activity. Down-regulation of SHPTP1 by ara-C was blocked by the PKCδ inhibitor rottlerin but not by the PKCα and -β inhibitor Gö6976. Moreover, transient coexpression studies with a dominant-negative mutant of PKCδ demonstrate that the kinase activity of PKCδ is required for the down-regulation of SHPTP1. These findings support the functional interaction between PKCδ and SHPTP1 in the cellular response to DNA damage.

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Molecular Pharmacology: 60 (6)
Molecular Pharmacology
Vol. 60, Issue 6
1 Dec 2001
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Research ArticleArticle

Negative Regulation of the SHPTP1 Protein Tyrosine Phosphatase by Protein Kinase C δ in Response to DNA Damage

Kiyotsugu Yoshida and Donald Kufe
Molecular Pharmacology December 1, 2001, 60 (6) 1431-1438; DOI: https://doi.org/10.1124/mol.60.6.1431

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Research ArticleArticle

Negative Regulation of the SHPTP1 Protein Tyrosine Phosphatase by Protein Kinase C δ in Response to DNA Damage

Kiyotsugu Yoshida and Donald Kufe
Molecular Pharmacology December 1, 2001, 60 (6) 1431-1438; DOI: https://doi.org/10.1124/mol.60.6.1431
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