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DHHC2 is a protein S-acyltransferase for Lck
Ruth Zeidman1, Gemma Buckland, Marek Cebecauer
1Molecular Medicine Section, National Heart & Lung Institute, Imperial College London, Sir Alexander Fleming Building, South Kensington, London, UK.
Molecular Membrane Biology
|November 1, 2011
Summary
The study identifies DHHC2 as the enzyme responsible for S-acylation of Lck (tyrosine kinase) in T cells. This finding is crucial for understanding T cell activation and Lck
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Lck (tyrosine kinase) is vital for T cell activation.
- Lck requires dual N-terminal acylation (myristate and palmitate) for membrane association and function.
- Reversible S-acylation of Lck suggests a regulatory mechanism.
Purpose of the Study:
- To identify the specific S-acyltransferase responsible for Lck palmitoylation in T cells.
- To investigate the role of DHHC2 in regulating Lck S-acylation and membrane localization.
Main Methods:
- Utilized siRNA to reduce DHHC2 levels in Jurkat T cells.
- Employed overexpression of DHHC2 with an Lck surrogate (LckN10-GFP).
- Assessed Lck S-acylation and membrane association via biochemical and imaging techniques.
Main Results:
- Identified DHHC2 as the S-acyltransferase that palmitoylates Lck in T cells.
- Reduced DHHC2 levels led to decreased Lck S-acylation and partial membrane dislocation.
- DHHC2 overexpression enhanced S-acylation of an Lck surrogate protein.
- DHHC2 was localized to the endoplasmic reticulum and Golgi apparatus.
Conclusions:
- DHHC2 is the primary enzyme mediating Lck S-acylation in T cells.
- DHHC2-mediated S-acylation regulates Lck membrane association and function.
- DHHC2 likely acts on newly synthesized or recycling Lck in the endoplasmic reticulum and Golgi apparatus, impacting T cell signaling.
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