DHHC2 is a protein S-acyltransferase for Lck.
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.
Molecular Medicine Section, National Heart & Lung Institute, Imperial College London, Sir Alexander Fleming Building, South Kensington, London, UK.
Ruth
R
Zeidman
Gemma
G
Buckland
Marek
M
Cebecauer
Philipp
P
Eissmann
Daniel M
DM
Davis
Anthony I
AI
Magee
D000215:Acylation; D000217:Acyltransferases / Q000737:chemistry / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000201:enzymology*; D015870:Gene Expression; D006056:Golgi Apparatus / Q000737:chemistry / Q000201:enzymology*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D054878:Lipoylation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000737:chemistry / Q000378:metabolism*; D019814:Myristic Acid / Q000737:chemistry / Q000378:metabolism; D010168:Palmitates / Q000737:chemistry / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D013601:T-Lymphocytes / Q000201:enzymology*; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000378:metabolism*
D010168:Palmitates; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; D019814:Myristic Acid; D000217:Acyltransferases; C532036:ZDHHC2 protein, human; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)