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Phosphorylation of CD3 and TCR zeta chains
Stable Identifier
R-HSA-202427
Type
Pathway
Species
Homo sapiens
Compartment
plasma membrane
ReviewStatus
5/5
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Phosphorylation of CD3 and TCR zeta chains (Homo sapiens)
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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. PAG bound CSK phosphorylates the negative regulatory tyrosine of LCK and inactivates the LCK kinase domain (step 1). CSK also inhibits PTPN22 by sequestering it via binding (step 2). Upon TCR stimulation, CSK dissociates from PAG1 (step 3) and PTPN22 (step4) and is unable to inhibit LCK. Furthermore, LCK becomes activated via PTPRC-mediated dephosphorylation of negative regulatory tyrosine residues (step 5). CD4/CD8 binds MHCII receptor in APC and the associated LCK co-localizes with the TCR. LCK is further activated by trans-autophosphorylation on the tyrosine residue on its activation loop (step 6). 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 7).
Literature References
PubMed ID
Title
Journal
Year
10375551
T cell antigen-receptor signal transduction
van Leeuwen, JE
,
Samelson, LE
Curr Opin Immunol
1999
Participants
Events
Interaction of Csk with PAG
(Homo sapiens)
Inactivation of Lck by Csk
(Homo sapiens)
Dephosphorylation of Lck-pY505 by CD45
(Homo sapiens)
Activation of Lck
(Homo sapiens)
PTPN22 dissociates from CSK
(Homo sapiens)
Inactivation of LCK by PTPN22
(Homo sapiens)
Phosphorylation of ITAM motifs in CD3 complexes
(Homo sapiens)
Participates
as an event of
TCR signaling (Homo sapiens)
Orthologous Events
Phosphorylation of CD3 and TCR zeta chains (Bos taurus)
Phosphorylation of CD3 and TCR zeta chains (Canis familiaris)
Phosphorylation of CD3 and TCR zeta chains (Danio rerio)
Phosphorylation of CD3 and TCR zeta chains (Gallus gallus)
Phosphorylation of CD3 and TCR zeta chains (Mus musculus)
Phosphorylation of CD3 and TCR zeta chains (Rattus norvegicus)
Phosphorylation of CD3 and TCR zeta chains (Sus scrofa)
Phosphorylation of CD3 and TCR zeta chains (Xenopus tropicalis)
Cross References
BioModels Database
BIOMD0000000724
Authored
Garapati, P V (2008-01-24)
Rudd, C.E. (2008-01-24)
de Bono, B (2008-01-24)
Reviewed
Trowsdale, J (2008-02-26)
Created
Garapati, P V (2007-10-29)
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