CD4, CD8 and the role of CD45 in T-cell activation.
CD4, CD8 and CD45 regulate the coupling of the T-cell receptor complex (CD3-TCR) to tyrosine kinase activation and phosphorylation of key substrates such as phospholipase C gamma 1. CD4 and CD8 contribute to activation signals through their cytoplasmic association with p56lck. Expression of the zeta-chain is required for functional synergy of the T-cell receptor with CD4 in the activation of phospholipase C gamma 1, which probably reflects an interaction between p56lck and zeta-associated kinase ZAP-70. CD45 expression is required for CD3-TCR signaling. CD45 may positively regulate signaling by dephosphorylating the carboxyl-terminal tyrosine of p56lck and p59fyn, and negatively regulate signaling by dephosphorylation of other TCR-associated substrates directly. One ligand for CD45 receptor has been identified as the B cell CD22 molecule. The positive and negative effects of CD45 are sensitive to the composition of CD45 in receptor complexes, and may be regulated by specific associations of CD45 isoforms with other receptors such as CD3-TCR, CD2 and CD4.
Ledbetter
J A
JA
Bristol-Myers Squibb-PRI, Seattle.
Deans
J P
JP
Aruffo
A
A
Grosmaire
L S
LS
Kanner
S B
SB
Bolen
J B
JB
Schieven
G L
GL
D000818:Animals; D015704:CD4 Antigens / Q000502:physiology*; D016827:CD8 Antigens / Q000502:physiology*; D004789:Enzyme Activation; D017493:Leukocyte Common Antigens / Q000502:physiology*; D008213:Lymphocyte Activation / Q000502:physiology*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D008565:Membrane Proteins / Q000502:physiology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051076:Proto-Oncogene Proteins c-fyn; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D010738:Type C Phospholipases / Q000502:physiology; D051746:ZAP-70 Protein-Tyrosine Kinase
D015704:CD4 Antigens; D016827:CD8 Antigens; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011948:Receptors, Antigen, T-Cell; C054979:antigen T cell receptor, zeta chain; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051076:Proto-Oncogene Proteins c-fyn; D051746:ZAP-70 Protein-Tyrosine Kinase; D017493:Leukocyte Common Antigens; D010738:Type C Phospholipases