Antigen receptor signaling pathways are regulated by a balanced equilibrium between tyrosine kinases and tyrosine phosphatases. In general, activation of signaling proceeds when the kinase activities leading to auto-phosphorylation of Lck, to phosphorylation of ZAP-70, and to phosphorylation of downstream adapters and scaffolds exceeds the activity of phosphatases acting on these substrates. Therefore, it came as a surprise when T cells lacking the membrane tyrosine phosphatase, CD45, were first generated, and were found to be unable to be activated by TCR stimulation. Name one important function of CD45 in T cells that explains the requirement for this phosphatase in TCR signaling.

Question

Quizplus · Accepted Answer

The Answer is CD45 is the phosphatase that de-phosphorylates the C-terminal negative regulatory tyrosine of Lck. When this negative regulatory tyrosine is phosphorylated and binds to the Lck SH2 domain, Lck is held in an inactive conformation. TCR signaling initiated by Lck cannot occur without CD45 to dephosphorylate this site.

Antigen Receptor Signaling Pathways Are Regulated by a Balanced Equilibrium