CD28 and the tyrosine kinase Lck stimulate mitogen-activated protein kinase activity in T cells via inhibition of the small G protein Rap1

K. D. Carey, T. J. Dillon, J. M. Schmitt, A. M. Baird, A. D. Holdorf, D. B. Straus, A. S. Shaw, P. J.S. Stork

Research output: Contribution to journalArticlepeer-review

73 Scopus citations

Abstract

Proliferation of T cells via activation of the T-cell receptor (TCR) requires concurrent engagement of accessory costimulatory molecules to achieve full activation. The best-studied costimulatory molecule, CD28, achieves these effects, in part, by augmenting signals from the TCR to the mitogen-activated protein (MAP) kinase cascade. We show here that TCR-mediated stimulation of MAP kinase extracellular-signal-regulated kinases (ERKs) is limited by activation of the Ras antagonist Rap1. CD28 increases ERK signaling by blocking Rap1 action. CD28 inhibits Rap1 activation because it selectively stimulates an extrinsic Rap1 GTPase activity. The ability of CD28 to stimulate Rap1 GTPase activity was dependent on the tyrosine kinase Lck. Our results suggest that CD28-mediated Rap1 GTPase-activating protein activation can help explain the augmentation of ERKs during CD28 costimulation.

Original languageEnglish (US)
Pages (from-to)8409-8419
Number of pages11
JournalMolecular and cellular biology
Volume20
Issue number22
DOIs
StatePublished - 2000

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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