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Tyrosine kinase 2 interacts with the proapoptotic protein Siva-1 and augments its apoptotic functions

Haruko K Shimoda1, Kotaro Shide, Takuro Kameda

  • 1Gastroenterology and Hematology, Faculty of Medicine, Miyazaki University, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan. hshimoda@fc.miyazaki-u.ac.jp

Biochemical and Biophysical Research Communications
|August 24, 2010
PubMed

Insights

The molecule Siva-1 induces apoptosis and binds to Tyrosine Kinase 2 (Tyk2). This interaction directly enhances Siva-1

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Immunology

Background:

  • Siva-1 is a known inducer of apoptosis through both extrinsic and intrinsic pathways.
  • Siva-1 interacts with CD27, Abl-related gene (ARG), and BCL-X(L), enhancing its apoptotic functions.

Purpose of the Study:

  • To investigate the interaction between Siva-1 and Tyrosine Kinase 2 (Tyk2).
  • To determine the functional consequence of the Siva-1 and Tyk2 interaction on apoptosis.

Main Methods:

  • Co-immunoprecipitation assays to confirm the interaction between Siva-1 and Tyk2.
  • Site-directed mutagenesis to identify phosphorylation sites on Siva-1.
  • Apoptosis assays in murine pro-B and Ba/F3 cells expressing Tyk2.

Main Results:

  • Siva-1 directly binds to Tyrosine Kinase 2 (Tyk2) via its N-terminal region.
  • Tyk2 phosphorylates Siva-1 at tyrosines 53 and 162.
  • Tyk2 expression augments Siva-1-induced apoptosis in Ba/F3 cells, independent of phosphorylation but dependent on the interaction.

Conclusions:

  • The interaction between Siva-1 and Tyk2 directly enhances Siva-1's apoptotic activity.
  • Siva-1 forms a functional complex with Tyk2, suggesting a role in inhibiting B lymphocyte growth.

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