Reviewed: Trowsdale, J, 2008-02-26 12:02:59 Authored: Rudd, C.E., de Bono, B, Garapati, P V, 2008-01-24 15:53:10 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. <p><br><br>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). <p><br><br>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).

http://purl.obolibrary.org/obo/HINO_0026235

Reviewed: Trowsdale, J, 2008-02-26 12:02:59

Authored: Rudd, C.E., de Bono, B, Garapati, P V, 2008-01-24 15:53:10

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).

Pubmed10375551

Reactome, http://www.reactome.org

Phosphorylation of CD3 and TCR zeta chains

http://purl.obolibrary.org/obo/NCBITaxon_9606

HINO:0026235

Phosphorylation of CD3 and TCR zeta chains

Reactome Database ID Release 43202427

ReactomeREACT_12582

http://purl.obolibrary.org/obo/INO_0000021

http://purl.obolibrary.org/obo/HINO_0017819

http://purl.obolibrary.org/obo/HINO_0017818

http://purl.obolibrary.org/obo/HINO_0017823

http://purl.obolibrary.org/obo/HINO_0017821

http://purl.obolibrary.org/obo/HINO_0017820