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The golli-myelin basic protein negatively regulates signal transduction in T lymphocytes

Ji-Ming Feng1, Augustine O Fernandes, Celia W Campagnoni

  • 1UCLA Medical School, Neuropsychiatric Institute, Room 47-448, 760 Westwood Plaza, Los Angeles, CA 90024-17519, USA. jfeng@mednet.ucla.edu

Journal of Neuroimmunology
|June 30, 2004
PubMed

Insights

Myelin basic protein (MBP) gene products, specifically golli BG21, act as negative regulators in T lymphocyte activation. This novel finding reveals a new role for MBP in immune system signaling pathways.

Area of Science:

  • Immunology
  • Cellular Signaling
  • Molecular Biology

Background:

  • Protein kinase C (PKC) is crucial for T lymphocyte activation.
  • Proper T lymphocyte activation requires both positive and negative regulatory signals.

Purpose of the Study:

  • To investigate the role of golli products from the myelin basic protein (MBP) gene in T lymphocyte signaling.
  • To determine if MBP gene products can act as negative regulators of T lymphocyte activation pathways, particularly the PKC pathway.

Main Methods:

  • Increased expression of golli BG21 in Jurkat T cells.
  • Assessed inhibition of anti-CD3-induced IL-2-luciferase activity.
  • Investigated in vitro phosphorylation of BG21 by PKC.
  • Analyzed effects on PMA-induced AP-1 and NF-kappaB activation.
  • Utilized mutant BG21 lacking PKC phosphorylation sites.
  • Performed structure-function assays to identify inhibitory domains.

Main Results:

  • Golli BG21 significantly inhibited anti-CD3-induced IL-2-luciferase activity in Jurkat T cells.
  • BG21 phosphorylation by PKC increased in activated cells.
  • BG21 inhibited PMA-induced AP-1 and NF-kappaB activation.
  • Inhibition occurred downstream of PKC activation, not affecting PKC enzyme activity or membrane association.
  • Phosphorylation-deficient BG21 mutant retained inhibitory function.
  • Inhibitory activity was localized to the golli domain of BG21.

Conclusions:

  • Golli products of the MBP gene, specifically BG21, function as negative regulators of T lymphocyte signaling pathways.
  • BG21 acts downstream of PKC activation and its inhibitory function is independent of direct PKC phosphorylation.
  • These findings reveal a novel role for MBP gene products in regulating T lymphocyte activation within the immune system.

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