Authentic Biochemistry

The Src-family kinase Lck regulates T-cell development, activation, proliferation, and immune synapse dynamics. These are the initiation phases of TCR  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.  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 phosphorylation of Tyr505, located at the C-terminus, by the tyrosine kinase Csk results in an inactive enzyme. References Longev Healthspan. 2012; 1: 6 SCIENCE ADVANCES•19 Jun 2019•Vol 5, Issue 6 --- Send in a voice message: https://anchor.fm/dr-daniel-j