Citation Details
Combined spatial and enzymatic regulation of Csk by cAMP and protein kinase A inhibits T cell receptor signaling
| Authors | Vang T, Abrahamsen H, Myklebust S, Horejesi V, Taskén K |
| In | J Biol Chem (2003) 278(20): 17597-17600 |
| Cells used in publication | T cell, human peripheral blood unstim. Unstimulated Human peripheral blood T cells Blood/Immune Cells Primary Cells Species: human Tissue Origin: blood |
| Substrate | Plasmid (general) |
| Research Area | Immunology / Hematology |
Nucleofection Experiments
Cyclic AMP (cAMP) inhibits TCR-induced T cell activation and thereby exerts important immunoregulatory functions. In this context, Csk, a ubiquitously expressed cytosolic PTK (protein tyrosine kinase) appears to be an important means of negative regulation of TCR signaling. Csk is recruited to rafts via its SH2 domain. Csk contains a catalytic kinase domain and transiently dissociates from lipid rafts upon TCR triggering. This publication is aimed at revealing the role of Csk in TCR-induced signaling by cAMP. Primary T cells were nucleofected with an empty plasmid or a plasmid encoding kinase deficient HA-tagged Csk-SH3-SH2, which has an intact and functional SH3 and SH2 domain but lacks the kinase domain. Cells were treated with PGE2 (prostaglandin E2) to elevate the intracellular cAMP level. The results indicated that the inhibitory effects of PGE2/cAMP on TCR signaling are dependent on the presence of Csk in rafts and/or the ability of recruiting additional amounts of Csk to rafts.
