Být, či nebýt aktivován: současný pohled na regulaci Lck v signalizaci proximálních T-buněk

Valečka, Jan

Src-family kinases are critical members of many signalling pathways present in many cell types. Lck, a member of this family of kinases, plays a crucial role in the initiation of T cell activation. An activation of Lck in T cells is one of the first biochemical events detectable after T cell receptor engagement. Kinase activity of Lck is regulated on several levels. Firstly, activity of Lck depends on phosphorylation status of positive and negative regulatory tyrosines that predicate structural conformation and kinase activity. Several kinases and phosphatases targeting Lck regulatory tyrosine residues have been already characterized. Another level of complexity in the regulation of Lck activity is mediated through interactions with adaptor proteins. A critical role in the regulation of Lck activity plays the cellular microenvironment, especially membrane microdomains called Lipid rafts. For a long time, it was assumed that ligand recognition by TCR triggers Lck activation what in turn initiates the downstream signalling. However this paradigm has been challenged as recent data point to the preexistence of a large fraction of Lck in activated state prior to TCR triggering and remains so during the first 2 - 5 minutes after activation. This novel finding poses new questions about the mechanisms that (i)...

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