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Characterization of a novel basic‐rich signaling motif found in the CD3 ε subunit of the T cell receptor
Author(s) -
DeFordWatts Laura M.,
Albanesi Joseph P.,
Murphy Tara,
Oers Nicolai S. C.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1064.8
Subject(s) - immunoreceptor tyrosine based activation motif , t cell receptor , microbiology and biotechnology , signal transduction , phosphorylation , cd3 , phosphoprotein , biology , t cell , protein subunit , receptor , tyrosine kinase , chemistry , cd8 , biochemistry , genetics , immune system , sh2 domain , gene
The T cell receptor (TCR) complex consists of the ligand‐binding α/β heterodimer as well as four associated signaling chains (CD3 γ, δ, ε, and ζ). Each of the CD3 subunits contains one or more copies of a signaling motif termed an immunoreceptor tyrosine‐based activation motif (ITAM). Phosphorylation of tyrosine residues within the ITAMs is critical for TCR‐mediated signaling events. We recently identified an additional signaling motif in the cytoplasmic tail of CD3 ε that we termed the basic‐rich stretch (BRS). Biochemical studies revealed that the BRS could complex the serine/threonine kinase G protein‐coupled receptor kinase 2 (GRK2). Interactions between the BRS and GRK2 likely contribute to TCR cross‐talk with G protein‐coupled receptors, such as CXCR4. To address the role of the BRS in T cell functions, we generated several murine CD3 ε transgenic lines bearing distinct mutations in the BRS. Preliminary results indicate that select modifications of the BRS can dramatically attenuate T cell development and/or alter phosphoprotein induction. Our findings suggest that in addition to its ITAM, CD3 ε contains a second signaling motif (the BRS) that is critical for T cell functions. [Work was supported by grants from NIAID 5T32AI005284 and AI042953]