Premium
Binding affinities of the SH2 domains of ZAP‐70, p 56 / ck and Shc to the chain ITAMs of the T‐cell receptor determined by surface plasmon resonance
Author(s) -
Labadia M. E.,
Ingraham R. H.,
SchembriKing J.,
Morelock M. M.,
Jakes S.
Publication year - 1996
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.59.5.740
Subject(s) - immunoreceptor tyrosine based activation motif , sh2 domain , biology , signal transduction , surface plasmon resonance , phosphorylation , tyrosine , affinities , tyrosine phosphorylation , phosphotyrosine binding domain , t cell receptor , microbiology and biotechnology , receptor , biochemistry , t cell , genetics , materials science , immune system , nanoparticle , nanotechnology
The chains of the T cell receptor complex play a critical role in the initiation of proximal signaling events upon T cell activation. Three pairs of potential tyrosine phosphorylation sites are located within the cytoplasmic domains of the chains. Subsequent to engagement of the T cell receptor, one or more of these tyrosine residues is phosphorylated. The phosphotyrosine residues, along with flanking amino acids, form an activation motif (and are shared by signaling subunits in the TCR, B cell receptor, and FcγRI) termed tyrosine‐based activation motifs (ITAMs). ITAMs serve as binding sites for SH2 domain‐containing proteins. Recent evidence suggests that the chains provide docking space for several key signal transduction molecules such as ZAP‐70, p 56 lck , and Shc. To determine if ZAP‐70, p 56 lck , and Shc bind to particular chain ITAM sequences, quantitative free‐solution measurements of binding affinities (K d ) were obtained by use of surface plasmon resonance technology. The results indicate that binding affinities of distinct SH2 domains to individual and paired phosphorylation sites greatly differ, and may dictate the sequence of signal transduction events.