DHHC2 is a protein S-acyltransferase for Lck

Abstract

Lck is a non-receptor tyrosine kinase of the Src family that is essential for T cell activation. Dual N-terminal acylation of Lck with myristate (N-acylation) and palmitate (S-acylation) is essential for its membrane association and function. Reversible S-acylation of Lck is observed in vivo and may function as a control mechanism. Here we identify the DHHC family protein S-acyltransferase DHHC2 as an enzyme capable of palmitoylating of Lck in T cells. Reducing the DHHC2 level in Jurkat T cells using siRNA causes decreased Lck S-acylation and partial dislocation from membranes, and conversely overexpression of DHHC2 increases S-acylation of an Lck surrogate, LckN10-GFP. DHHC2 localizes primarily to the endoplasmic reticulum and Golgi apparatus suggesting that it is involved in S-acylation of newly-synthesized or recycling Lck involved in T cell signalling.

Keywords::

• Palmitoylation
• tyrosine kinase
• signalling
• T lymphocytes

Acknowledgements

We thank Dr E. Jury, University College London, for the kind gift of primary human B cells. Work in the Magee laboratory was supported by grants G0100471 and G0400710 from the UK Medical Research Council. D.M. Davis wishes to acknowledge an EMBO Young Investigator award. We thank the Facility for Imaging by Light Microscopy (FILM) for access to fluorescence microscopes and advice.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.