The Cbl family and other ubiquitin ligases: Destructive forces in control of antigen receptor signaling

Lei Duan, Alagarsamy Lakku Reddi, Amiya Ghosh, Manjari Dimri, Hamid Band

Research output: Contribution to journalReview article

98 Scopus citations

Abstract

Regulation of tyrosine kinase-mediated cellular activation through antigen receptors is of great biological and practical significance. The evolutionarily conserved Cbl family ubiquitin ligases have emerged as key negative regulators of activated tyrosine kinase-coupled receptors, and their impaired function switches a normal immune response into autoimmunity. Cbl proteins facilitate the ubiquitinylation of activated tyrosine kinases and other signaling proteins and of the signaling chains of receptors themselves; monoubiquitin tag promotes sorting of activated receptors and associated proteins into internal vesicles of the multivesicular body, facilitating their lysosomal degradation, whereas polyubiquitin tag promotes proteasomal degradation. Notably, increased expression of Cbl proteins and other ubiquitin ligases is a component of anergic signaling program in T cells. Thus, controlled destruction of the signaling apparatus has emerged as a key to fine-tuning antigen receptor signaling. Further studies of this pathway are likely to elucidate the pathogenesis of autoimmune diseases and offer new therapeutic targets.

Original languageEnglish (US)
Pages (from-to)7-17
Number of pages11
JournalImmunity
Volume21
Issue number1
DOIs
StatePublished - Jul 1 2004

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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