CSK associates with the TCR zeta and epsilon chains via its SH2 domain; a mechanism for turning off TCR signaling.
Recent biochemical and genetic studies implicate Csk (carboxy-terminal Src kinase) as the one of the main downregulators of the activity of members of the Src family of kinases. Csk is probably involved in the downregulation of TCR signaling by C-terminal tyrosine phosphorylation of Lck and Fyn, but the mechanism whereby Csk targets these Src family members is not known. Here we report the association of Csk with the TCR complex, an interaction mediated by the binding of the Csk-SH2 domain to phosphorylated zeta and epsilon chains of the TCR complex. The interaction with TCR brings Csk into close contact with Lck and Fyn which are known to be associated with TCR, either functionally and/or physically. This finding suggests a novel mechanism whereby TCR signaling is turned off.
Catipović
B
B
Division of Clinical Immunology, Johns Hopkins Asthma and Allergy Center, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
D000818:Animals; D000081247:CSK Tyrosine-Protein Kinase; D002460:Cell Line; D015536:Down-Regulation; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology*; D010766:Phosphorylation; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism; D018909:src Homology Domains; D019061:src-Family Kinases
D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; C061836:antigen T cell receptor, epsilon chain; C054979:antigen T cell receptor, zeta chain; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human