The Membrane-proximal Portion of CD3 ϵ Associates with the Serine/Threonine Kinase GRK2

• Published in: The Journal of biological chemistry 2007-06, Vol.282 (22), p.16126
• Main Authors: Laura M. DeFord-Watts, Jennifer A. Young, Lisa A. Pitcher, Nicolai S. C. van Oers
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M609418200

The activation of protein kinases is one of the primary mechanisms whereby T cell receptors (TCR) propagate intracellular signals. To date, the majority of kinases known to be involved in the early stages of TCR signaling are protein-tyrosine kinases such as Lck, Fyn, and ZAP-70. Here we report a constitutive association between the TCR and a serine/threonine kinase, which was mediated through the membrane-proximal portion of CD3 ϵ. Mass spectrometry analysis of CD3 ϵ-associated proteins identified G protein-coupled receptor kinase 2 (GRK2) as a candidate Ser/Thr kinase. Transient transfection assays and Western blot analysis verified the ability of GRK2 to interact with the cytoplasmic domain of CD3 ϵ within a cell. These findings are consistent with recent reports demonstrating the ability of certain G protein-coupled receptors (GPCR) and G proteins to physically associate with the α/β TCR. Because GRK2 is primarily involved in arresting GPCR signals, its interaction with CD3 ϵ may provide a novel means whereby the TCR can negatively regulate signals generated through GPCRs.