The membrane-proximal portion of CD3 ε associates with the serine/threonine kinase GRK2

Laura M. DeFord-Watts, Jennifer A. Young, Lisa A. Pitcher, Nicolai S C Van Oers

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)16126-16134
Number of pages9
JournalJournal of Biological Chemistry
Volume282
Issue number22
DOIs
StatePublished - Jun 1 2007

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G-Protein-Coupled Receptor Kinase 2
Protein-Serine-Threonine Kinases
T-Cell Antigen Receptor
Membranes
G-Protein-Coupled Receptors
Phosphotransferases
Receptor Protein-Tyrosine Kinases
GTP-Binding Proteins
Protein-Tyrosine Kinases
Protein Kinases
Transfection
Mass spectrometry
Assays
Mass Spectrometry
Western Blotting
Chemical activation
Association reactions
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

The membrane-proximal portion of CD3 ε associates with the serine/threonine kinase GRK2. / DeFord-Watts, Laura M.; Young, Jennifer A.; Pitcher, Lisa A.; Van Oers, Nicolai S C.

In: Journal of Biological Chemistry, Vol. 282, No. 22, 01.06.2007, p. 16126-16134.

Research output: Contribution to journalArticle

DeFord-Watts, Laura M. ; Young, Jennifer A. ; Pitcher, Lisa A. ; Van Oers, Nicolai S C. / The membrane-proximal portion of CD3 ε associates with the serine/threonine kinase GRK2. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 22. pp. 16126-16134.
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