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Podcast: Authentic Biochemistry
Episode: T cell receptor signaling kinase dynamics after APC activation. Co-activating CD28 becomes deficient via immunosenescence thus corrupting T cell efficiency in the elderly. 26.10.2021 DJGPhD.
Description: The Src-family kinase Lck regulates T-cell development, activation, proliferation, and immune synapse dynamics. These are the initiation phases of TCR Â signaling. Upon antigen presentation via the APC- TCR immune synapse, Lck phosphorylates tyrosine residues within the immunoreceptor tyrosine-based activation motifs (ITAMs) of the TCR-associated CD3 membrane protein domains.
 Phosphorylated ITAMs function as a molecular platform  for  tandem SH2 domains located on  the tyrosine kinase Zap-70, initially activated by Lck.Â
Lck kinase activity is regulated at  two canonical  phosphorylation sites Tyr394 and Tyr505, wherein auto-transphosphorylation of Tyr394 in the kinase domain erupts a relaxed/active conformation but phos...