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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

Negative control of apoptosis signal-regulating kinase 1 through phosphorylation of Ser-1034

Katsunori Fujii1, Erinn Hoag Goldman, Hae Ryoun Park

  • 1Department of Pharmacology, Emory University School of Medicine, Atlanta GA 30322, USA.

Oncogene
|April 20, 2004
PubMed

Insights

Researchers discovered a new phosphorylation site on Apoptosis signal-regulating kinase 1 (ASK1) at Ser-1034. This finding reveals a novel mechanism for controlling ASK1

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Apoptosis signal-regulating kinase 1 (ASK1) is a key mediator of cellular stress responses.
  • ASK1 activity is tightly regulated through phosphorylation, with known sites at Thr-845 (activation) and Ser-967 (inhibition).

Purpose of the Study:

  • To identify novel regulatory phosphorylation sites on ASK1.
  • To elucidate the role of these sites in controlling ASK1 activity and proapoptotic function.

Main Methods:

  • Site-directed mutagenesis to create non-phosphorylatable ASK1 mutants (Ser-1034 to Ala).
  • In vitro kinase assays to measure catalytic activity.
  • Assessment of proapoptotic function in cellular models.

Main Results:

  • Identification of a novel phosphorylation site at Ser-1034 in the C-terminal regulatory domain of ASK1.
  • Mutation of Ser-1034 to Ala resulted in increased ASK1 catalytic activity.
  • The Ser-1034Ala mutation enhanced the proapoptotic function of ASK1.

Conclusions:

  • Phosphorylation at Ser-1034 negatively regulates ASK1 activity and its proapoptotic function.
  • This novel regulatory site suggests a mechanism where upstream survival kinases may modulate ASK1's death-promoting activity.

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