TCR crosslinking promotes Crk adaptor protein binding to tyrosine-phosphorylated CD3ζ chain

Guangyu Dong, Rachel Kalifa, Pulak Ranjan Nath, Sigal Gelkop, Noah Isakov

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

T cell antigen receptor (TCR) binding of a peptide antigen presented by antigen-presenting cells (APCs) in the context of surface MHC molecules initiates signaling events that regulate T cell activation, proliferation and differentiation. A key event in the activation process is the phosphorylation of the conserved tyrosine residues within the CD3 chain immunoreceptor tyrosine-based activation motifs (ITAMs), which operate as docking sites for SH2 domain-containing effector proteins. Phosphorylation of the CD3ζ ITAMs renders the CD3 chain capable of binding the ζ-chain associated protein 70 kDa (ZAP70), a protein tyrosine kinase that is essential for T cell activation. We found that TCR/CD3 crosslinking in Jurkat T cells promotes the association of Crk adaptor proteins with the transiently phosphorylated CD3ζ chain. Pull down assays using bead-immobilized GST fusion proteins revealed that the Crk-SH2 domain mediates binding of phospho-CD3ζ. Phospho-CD3ζ binding is selective and is mediated by the three types of Crk, including CrkI, CrkII, and CrkL, but not by other SH2 domain-containing adaptor proteins, such as Grb2, GRAP and Nck. Crk interaction with phospho-CD3ζ is rapid and transient, peaking 1 min post TCR/CD3 crosslinking. The results suggest the involvement of Crk adaptor proteins in the early stages of T cell activation in which Crk might help recruiting effector proteins to the vicinity of the phospho-CD3ζ and contribute to the fine-tuning of the TCR/CD3-coupled signal transduction pathways.

Original languageEnglish
Pages (from-to)541-546
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume488
Issue number3
DOIs
StatePublished - 1 Jul 2017

Keywords

  • CD3ζ chain
  • Crk adaptor proteins
  • Signal transduction
  • T cell activation
  • TCR/CD3 crosslinking
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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