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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acylation
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Acyltransferases / chemistry
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Acyltransferases / metabolism*
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Endoplasmic Reticulum / chemistry
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Endoplasmic Reticulum / enzymology*
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Gene Expression
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Golgi Apparatus / chemistry
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Golgi Apparatus / enzymology*
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HEK293 Cells
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HeLa Cells
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Humans
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Jurkat Cells
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Lipoylation
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / chemistry
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / metabolism*
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Myristic Acid / chemistry
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Myristic Acid / metabolism
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Palmitates / chemistry
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Palmitates / metabolism
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RNA, Small Interfering / genetics
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T-Lymphocytes / enzymology*
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Tumor Suppressor Proteins / chemistry
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Tumor Suppressor Proteins / metabolism*
Substances
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Palmitates
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RNA, Small Interfering
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Tumor Suppressor Proteins
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Myristic Acid
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Acyltransferases
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ZDHHC2 protein, human
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck)