Zeidman Ruth, Buckland Gemma, Cebecauer Marek, Eissmann Philipp, Davis Daniel M, Magee Anthony I
Molecular Medicine Section, National Heart & Lung Institute, Imperial College London, Sir Alexander Fleming Building, South Kensington, London, UK.
Mol Membr Biol. 2011 Oct-Nov;28(7-8):473-86. doi: 10.3109/09687688.2011.630682.
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.
Lck是Src家族的一种非受体酪氨酸激酶，对T细胞活化至关重要。Lck的N端双酰化，即肉豆蔻酸（N-酰化）和棕榈酸（S-酰化）修饰，对其膜结合及功能至关重要。Lck的S-酰化在体内是可逆的，可能起到一种调控机制的作用。在此，我们鉴定出DHHC家族蛋白S-酰基转移酶DHHC2是一种能够使T细胞中的Lck发生棕榈酰化的酶。使用小干扰RNA降低Jurkat T细胞中的DHHC2水平会导致Lck的S-酰化减少以及从膜上部分错位，相反，过表达DHHC2会增加Lck替代物LckN10-GFP的S-酰化。DHHC2主要定位于内质网和高尔基体，这表明它参与了T细胞信号传导中新生或循环利用的Lck的S-酰化过程。
