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Protein phosphatase type 2C dephosphorylates BAD

Susanne Klumpp1, Dagmar Selke, Josef Krieglstein

  • 1Institut für Pharamzeutische und Medizinische Chemie, Westfälische Wilhelms-Universität, Hittorfstrasse 58-62, 48149 Münster, Germany. klumpp@uni-muenster.de

Neurochemistry International
|February 20, 2003
PubMed

Insights

Protein phosphatase 2C (PP2C) dephosphorylates BAD at Serine 155, promoting apoptosis. This finding reveals PP2C as a key regulator of cell death decisions by influencing BAD

Area of Science:

  • Cellular biology
  • Molecular biology
  • Biochemistry

Background:

  • Reversible phosphorylation regulates cellular apoptosis susceptibility.
  • The phosphorylation state of BAD, a Bcl-2 family protein, is critical for cell fate decisions.
  • Phosphorylation of BAD at Ser112, Ser136, and Ser155 inhibits apoptosis.

Purpose of the Study:

  • To investigate the role of protein phosphatase 2C (PP2C) in BAD phosphorylation and apoptosis.
  • To determine the substrate specificity of PP2C on different phosphorylated sites of BAD.
  • To elucidate the impact of PP2C-mediated dephosphorylation of BAD on its pro-apoptotic function.

Main Methods:

  • In vitro phosphatase assays using purified BAD and various phosphatases (PP1, PP2A, PP2C).
  • Analysis of BAD phosphorylation status using specific antibodies and mass spectrometry.
  • Assessment of BAD's interaction with Bcl-X(L) following dephosphorylation.

Main Results:

  • BAD is identified as a substrate for PP2C.
  • PP2C preferentially dephosphorylates P-Ser155 on BAD over P-Ser112 and P-Ser136.
  • Dephosphorylation of Ser155 by PP2C is crucial for BAD's pro-apoptotic activity and its heterodimerization with Bcl-X(L).

Conclusions:

  • PP2C plays a significant role in promoting apoptosis by dephosphorylating BAD at Ser155.
  • PP2C acts as a critical regulator of cell survival by modulating BAD's function.
  • The specific dephosphorylation of P-Ser155 by PP2C highlights a novel mechanism in the control of apoptosis.

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