TY - JOUR
T1 - The membrane-proximal portion of CD3 ε associates with the serine/threonine kinase GRK2
AU - DeFord-Watts, Laura M.
AU - Young, Jennifer A.
AU - Pitcher, Lisa A.
AU - Van Oers, Nicolai S C
PY - 2007/6/1
Y1 - 2007/6/1
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M609418200
DO - 10.1074/jbc.M609418200
M3 - Article
C2 - 17420248
AN - SCOPUS:34447501764
SN - 0021-9258
VL - 282
SP - 16126
EP - 16134
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 22
ER -