Key role of ERK pathway signaling in lupus

Autoimmunity. 2010 Feb;43(1):17-22. doi: 10.3109/08916930903374832.


Systemic lupus erythematosus is a poorly understood autoimmune disease, characterized by autoantibodies to nuclear antigens and immune complex deposition in organs like the kidney. Current evidence indicates that a pathologic CD4+T cell subset, characterized by impaired extracellular signal-regulated kinase (ERK) pathway signaling, DNA hypomethylation, and consequent aberrant gene expression contributes to disease pathogenesis. Hydralazine is a lupus-inducing drug that also decreases T cell DNA methylation by inhibiting the ERK signaling pathway, replicating the defect found in lupus T cells. These observations suggest that defective ERK pathway signaling alters gene expression in T cells by inhibiting DNA methylation, contributing to lupus pathogenesis. The signaling defect in hydralazine-treated and lupus T cells has now been mapped to protein kinase C delta. Understanding the mechanism causing decreased ERK pathway signaling in lupus may shed light on mechanisms contributing to disease development in genetically predisposed people.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • CD4-Positive T-Lymphocytes / enzymology
  • CD4-Positive T-Lymphocytes / immunology
  • DNA Methylation
  • Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Humans
  • Lupus Erythematosus, Systemic / enzymology*
  • Lupus Erythematosus, Systemic / genetics
  • Lupus Erythematosus, Systemic / immunology
  • MAP Kinase Signaling System*
  • Protein Kinase C-delta / immunology
  • Protein Kinase C-delta / metabolism


  • Protein Kinase C-delta
  • Extracellular Signal-Regulated MAP Kinases