Two distinct regions of the CD28 intracytoplasmic domain are involved in the tyrosine phosphorylation of Vav and GTPase activating protein-associated p62 protein

Sandrine Klasen, Françoise Pages, Jean François Peyron, Doreen A. Cantrell, Daniel Olive (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    49 Citations (Scopus)

    Abstract

    The T cell-associated CD28 molecule plays a key role in T cell co-stimulation. Its ligation induces the tyrosine phosphorylation of numerous proteins including CD28 itself as well as a restricted set of substrates of 97 and 62-68 kDa which are poorly phosphorylated by the tyrosine kinases induced by CD3-TCR triggering. In this study, we identify these substrates as the product of the vav proto-oncogene and as a 62 kDa protein that could correspond at least in part to p62dok, the 62 kDa adaptor molecule associated to p120 Ras-GTPase activating protein. Both p97vav and p62 are tyrosine phosphorylated upon CD28 ligation by mAb or by its counter-receptor B7-1/CD80. Using CD28 mutants, we also show that Vav and p62 tyrosine phosphorylation is regulated by distinct domains within the CD28 cytoplasmic tail: residues 173-181 for Vav and residues 182-202 for p62. Finally, the phosphorylation of Vav and p62 does not require an intact binding site for Grb-2 or p85 SH2 domains. We thus demonstrate that the CD28 cytoplasmic domain contains at least three functionally independent regions involved in CD28-induced signal transduction, since in addition to the Grb-2 and p85 SH2 domain binding site (Tyr173), residues 173-181 and 182-202 are associated with Vav and p62 tyrosine phosphorylation respectively.

    Original languageEnglish
    Pages (from-to)481-489
    Number of pages9
    JournalInternational Immunology
    Volume10
    Issue number4
    DOIs
    Publication statusPublished - 1 Apr 1998

    Keywords

    • Signal transduction
    • T cell co-stimulation

    Fingerprint Dive into the research topics of 'Two distinct regions of the CD28 intracytoplasmic domain are involved in the tyrosine phosphorylation of Vav and GTPase activating protein-associated p62 protein'. Together they form a unique fingerprint.

    Cite this