Association between mitogen-activated protein kinase and the ζ chain of the T cell receptor (TcR) with the SH2,3 domain of p56lck: Differential regulation by TcR cross-linking

Avery August, Bo Dupont

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A number of protein-tyrosine kinases have been shown to be important in T cell activation. One such kinase, Lck, has been demonstrated genetically to be essential for T cell receptor (TcR) signaling, and the SH2 and SH3 (src homology 2 and 3) domains of Lck have been shown to be indispensable for T cell activation. We have sought substrates with which the SH2,3 domain would interact following T cell activation, using fusion proteins containing the Lck SH2 and SH3 domains linked to glutathione S-transferase. We demonstrate that the SH2,3 region interacts specifically and directly with numerous tyrosine-phosphorylated molecules following TcR cross-linking, including constitutively with mitogen-activated protein kinase (MAPK)/extracellular-regulated kinase and inducibly with the ζ chain of the TcR. The interaction with MAPK/extracellular-regulated kinase was via the SH3 domain. The interaction with the tyrosine-phosphorylated ζ chain, while phosphotyrosine-dependent, required both the SH3 and SH2 domains. These interactions were specific as molecules known to be tyrosine-phosphorylated following TcR cross-linking, phospholipase C-γ1 and Fyn, were not bound. Thus, we suggest that during TcR signaling, Lck interacts with numerous molecules, including MAPK and TcR-ζ, via its SH2,3 domain. The interaction with MAPK would place Lck in a position to be involved in the complex resulting in the activation of MAPK. In addition, the binding of Lck to the tyrosine-phosphorylated ζ chain of the TcR would serve to strengthen the interaction of the associated CD4 and the TcR complex, leading to increased avidity for the antigen-major histocompatibility protein complex.

Original languageEnglish (US)
Pages (from-to)10054-10059
Number of pages6
JournalJournal of Biological Chemistry
Issue number17
StatePublished - Apr 26 1996

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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