Defective activity of ERK-1 and ERK-2 mitogen-activated protein kinases in peripheral blood T lymphocytes from patients with systemic lupus erythematosus: Potential role of altered coupling of Ras guanine nucleotide exchange factor hSos to adapter protein Grb2 in lupus T cells

Academic Article

Abstract

  • The integrity of the Ras/Raf/mitogen-activated protein kinase (MAPK) cascade is critical for maintenance of T cell tolerance, a process that fails in patients with systemic lupus erythematosus (SLE). In this study we have examined the activity of mitogen-activated protein kinases ERK-1 and ERK-2 in resting and TCR-activated peripheral blood T lymphocytes from patients with SLE. We also examined the binding of Ras guanine nucleotide exchange factor, human Son of Sevenless (hSos), to cytosolic adapter protein growth factor receptor-bound protein 2. T cells from lupus patients showed diminished catalytic activity and TCR-driven dual phosphorylation of ERK-1 and ERK-2 upon stimulation through the TCR/CD3 receptor, a defect that may be related to altered translocation of hSos to the Ras/Raf membrane complex and diminished nuclear translocation of trans-acting factor AP-1. Defective MAPK activity triggered by TCR/ CD3 activation may alter the coordination of signals needed for normal interleukin-2 production and maintenance of tolerance in lupus T cells. © 2003 Elsevier Science (USA). All rights reserved.
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    Digital Object Identifier (doi)

    Author List

  • Cedeño S; Cifarelli DF; Blasini AM; Paris M; Placeres F; Alonso G; Rodriguez MA
  • Start Page

  • 41
  • End Page

  • 49
  • Volume

  • 106
  • Issue

  • 1