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The chaperone protein 14-3-3 interacts with 3BP2/SH3BP2 and regulates its adapter function
Isabelle Foucault1, Yun-Cai Liu, Alain Bernard
1INSERM U343 and Laboratoire d'Immunologie, Hôpital de l'Archet I, Nice 06202, France.
The Journal of Biological Chemistry
|December 27, 2002
Summary
The adapter protein 3BP2 interacts with 14-3-3 proteins in lymphocytes, a process regulated by phosphorylation. This binding negatively controls 3BP2
Area of Science:
- Immunology
- Molecular Biology
- Cell Signaling
Background:
- Lymphocyte activation involves complex signaling pathways.
- Adapter proteins like 3BP2 integrate these pathways.
- The precise mechanisms of 3BP2 regulation were unclear.
Purpose of the Study:
- To investigate the molecular mechanisms of 3BP2 in lymphocyte signaling.
- To identify interacting partners of 3BP2.
- To elucidate how 3BP2's function is regulated.
Main Methods:
- Yeast two-hybrid analysis.
- Biochemical assays.
- Mammalian cell studies.
- Analysis of deletion mutants.
Main Results:
- Direct physical interaction between 3BP2 and 14-3-3 proteins was confirmed.
- Phosphorylation of 3BP2 by kinases like Protein Kinase C is crucial for 14-3-3 binding.
- Two specific proline-rich domains in 3BP2 (residues 201-240 and 270-310) mediate 14-3-3 interaction.
- Serine residues Ser(225) and Ser(277) are essential for this interaction and 3BP2 function.
- A mutant 3BP2 unable to bind 14-3-3 showed enhanced NFAT transcriptional activity.
Conclusions:
- 14-3-3 proteins bind directly to 3BP2 in a phosphorylation-dependent manner.
- This binding negatively regulates the adapter function of 3BP2 in lymphocytes.
- Understanding this interaction provides insights into lymphocyte activation signaling.