The membrane-proximal portion of CD3 epsilon associates with the serine/threonine kinase GRK2.
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 epsilon. Mass spectrometry analysis of CD3 epsilon-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 epsilon 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 alpha/beta TCR. Because GRK2 is primarily involved in arresting GPCR signals, its interaction with CD3 epsilon may provide a novel means whereby the TCR can negatively regulate signals generated through GPCRs.
DeFord-Watts
Laura M
LM
Department of Immunology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9093, USA.
Young
Jennifer A
JA
Pitcher
Lisa A
LA
van Oers
Nicolai S C
NS
D000818:Animals; D017252:CD3 Complex / Q000235:genetics / Q000378:metabolism*; D054769:G-Protein-Coupled Receptor Kinase 2; D006801:Humans; D019169:Jurkat Cells; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D051379:Mice; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism; D051552:beta-Adrenergic Receptor Kinases / Q000235:genetics / Q000378:metabolism*
D017252:CD3 Complex; C485468:Cd3e protein, mouse; D016693:Receptors, Antigen, T-Cell, alpha-beta; D043562:Receptors, G-Protein-Coupled; C494960:Fyn protein, mouse; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051076:Proto-Oncogene Proteins c-fyn; D051746:ZAP-70 Protein-Tyrosine Kinase; C497262:Zap70 protein, mouse; C496568:GRK2 protein, mouse; D051552:beta-Adrenergic Receptor Kinases; D054769:G-Protein-Coupled Receptor Kinase 2