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Tyrosine phosphorylation and activation of Janus kinase 1 and STAT3 by sublytic C5b-9 complement complex in aortic

F Niculescu1, L Soane, T Badea

  • 1Department of Pathology, University of Maryland School of Medicine, Baltimore 21201, USA. fnicules@umaryland.edu

Immunopharmacology
|July 17, 1999
PubMed

Insights

Membrane-inserted C5b-9 activates Janus kinase 1 (JAK1) and signal transducer of transcription 3 (STAT3) in human aortic endothelial cells. This identifies a novel signaling pathway involving G proteins, Raf-1, and ERK1, regulating gene activation.

Area of Science:

  • Cellular signaling
  • Molecular biology
  • Immunology

Background:

  • The Janus kinase (JAK) and signal transducers and activators of transcription (STATs) pathway is crucial for cell differentiation and proliferation.
  • Receptor activation initiates cellular responses, but the role of complement component C5b-9 in this pathway is not fully understood.

Purpose of the Study:

  • To identify JAK and STAT proteins activated by C5b-9 in human aortic endothelial cells (AEC).
  • To elucidate the signaling mechanisms downstream of C5b-9 activation in AEC.

Main Methods:

  • Human aortic endothelial cells (AEC) were treated with sublytic C5b-9.
  • Tyrosine phosphorylation of JAK1, JAK2, and STAT3 was assessed.
  • The effect of Pertussis toxin on C5b-9 induced signaling was evaluated.
  • Nuclear translocation of STAT3 and activation of Raf-1 and ERK1 were analyzed.

Main Results:

  • Sublytic C5b-9 induced tyrosine phosphorylation of JAK1 and STAT3 in AEC.
  • JAK1 activation was inhibited by Pertussis toxin, suggesting G protein involvement (Gi/Go family).
  • STAT3 phosphorylation was not inhibited by Pertussis toxin, but C5b-9 induced its nuclear translocation.
  • C5b-9 also activated Raf-1 and ERK1 in a G protein-dependent manner.

Conclusions:

  • Membrane-inserted C5b-9 activates JAK1 and STAT3 in human AEC.
  • C5b-9 initiates signaling through G proteins, leading to JAK1 activation and subsequent activation of Raf-1 and ERK1.
  • This study defines a novel signaling pathway by which C5b-9 regulates gene activation in endothelial cells.

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