Reactome: A Curated Pathway Database

Phosphorylation of CD3 and TCR zeta chains (R-HSA-202427) [Homo sapiens]


Prior to T cell receptor (TCR) stimulation, CD4/CD8 associated Lck remains seperated from the TCR and is maintained in an inactive state by the action of Csk. Csk phosphorylates the negative regulatory tyrosine of Lck and inactivates the Lck kinase domain.

Upon TCR stimulation, CD4/CD8 associated Lck co-localizes with the TCR leading to the phosphorylation of the CD3 and TCR subunit. Lck becomes activated by way of CD45-mediated dephosphorylation of negative regulatory tyrosine residues. The presence to PAG-bound Csk is further reduced via the dephosphorylation of PAG (step 1).

Lck is further activated by trans-autophosphorylation on the tyrosine residue on its activation loop (step 2). Active Lck further phosphorylates the tyrosine residues on CD3 chains. The signal-transducing CD3 delta/epsilon/gamma and TCR zeta chains contain a critical signaling motif known as the immunoreceptor tyrosine-based activation motif (ITAM). The two critical tyrosines of each ITAM motif are phosphorylated by Lck (step 3).

Additional Information
Compartment plasma membrane
Literature References
pubMedId Title Journal Year
10375551 T cell antigen-receptor signal transduction Curr Opin Immunol 1999