Protein acylation and localization in T cell signaling (Review)

Many proteins with pivotal roles in T cell activation are modified by fatty acylation. Examples of these include transmembrane proteins such as the co-receptors CD4 and CD8, the adaptors LAT and Cbp/PAG, the pre-TCR as well as proteins synthesized on free cytosolic ribosomes, such as the Src-related tyrosine kinases Lck and Fyn. The two main types of fatty acylations in eukaryotic cells are N-myristoylation and S-acylation, the latter being more commonly referred to as palmitoylation. N-Myristoylation occurs exclusively on proteins synthesized on soluble ribosomes and provides substrates with an affinity for membranes. Palmitoylation modifies a wide range of substrates that includes both cytosolic and transmembrane proteins, its functions are diverse and in many cases not yet understood. Like myristoylation, palmitoylation promotes membrane-binding of cytosolic proteins, but it has also been implicated in protein targeting, trafficking, stability and activity. In addition, many palmitoylated proteins are insoluble in cold non-ionic detergent, and have therefore been proposed to localize to lipid rafts. The organization of receptors and signaling proteins into microdomains such as lipid rafts provides an attractive model for the initiation and propagation of T cell signaling, although many aspects of this are still poorly understood. This review will discuss the current evidence for the involvement of acylations in the localizations and functions of T cell signaling proteins.