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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

cGMP-dependent protein kinase I promotes cell apoptosis through hyperactivation of death-associated protein kinase 2

Kinuka Isshiki1, Shinya Matsuda, Akihiko Tsuji

  • 1Department of Biological Science and Technology, The University of Tokushima Graduate School, Tokushima 770-8506, Japan.

Biochemical and Biophysical Research Communications
|May 15, 2012
PubMed

Insights

Cyclic GMP-dependent protein kinase-I (cGK-I) triggers cancer cell death by phosphorylating death-associated protein kinase 2 (DAPK2). A specific DAPK2 mutation enhanced apoptosis, identifying DAPK2 as a key mediator in cGK-I-induced cancer cell death.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Cyclic GMP-dependent protein kinase-I (cGK-I) is known to induce apoptosis in cancer cells.
  • The precise molecular mechanisms underlying cGK-I-mediated apoptosis are not fully understood.

Purpose of the Study:

  • To identify novel substrates of cGK-I involved in apoptosis.
  • To elucidate the role of death-associated protein kinase 2 (DAPK2) in cGK-I-induced apoptosis.

Main Methods:

  • Protein microarray analysis was employed to identify cGK-I substrates.
  • Site-directed mutagenesis was used to create phospho-mimic mutants of DAPK2.
  • Apoptosis assays were performed in human breast cancer MCF-7 cells.

Main Results:

  • Death-associated protein kinase 2 (DAPK2) was identified as a novel substrate of cGK-I.
  • cGK-I phosphorylated DAPK2 at serine residues 299, 367, and 368.
  • A phospho-mimic mutant DAPK2 (S299D) exhibited enhanced kinase activity and significantly increased apoptosis in MCF-7 cells.

Conclusions:

  • DAPK2 is a novel target of cGK-I in the induction of apoptosis.
  • Phosphorylation of DAPK2 at Ser299 by cGK-I is critical for enhancing its kinase activity and promoting apoptosis in breast cancer cells.

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