F. Niculescu et al., Tyrosine phosphorylation and activation of Janus kinase 1 and STAT3 by sublytic C5b-9 complement complex in aortic endothelial cells, IMMUNOPHARM, 42(1-3), 1999, pp. 187-193
The pathway involving Janus kinase (JAK) and signal transducers and activat
ors of transcription (STATs) plays an important role in differentiation and
proliferation of-cells initiated by receptor activation. In the present st
udy we identified the JAK and STAT proteins activated by C5b-9 in human aor
tic endothelial cells (AEC). JAK1 but not JAK2 was tyrosine phosphorylated
in response to sublytic C5b-9. STAT3 was rapidly tyrosine phosphorylated al
so by C5b-9. Pertussis toxin inhibited the C5b-9 induced JAK1 activation. H
owever, phosphorylation of STAT3 was not inhibited by Pertussis toxin, alth
ough C5b-9 induced a time-dependent nuclear translocation of STAT3. These o
bservations indicated that JAK1 is phosphorylated by C5b-9 through activati
on of trimeric G proteins of the Gi/Go family. Raf-1 and ERK1 were also act
ivated by C5b-9 in human AEC in a G protein dependent manner. Therefore, JA
K1 activity may be involved in activation of Raf-l and ERK1 via G proteins
activated by C5b-9. This study demonstrates the ability of membrane-inserte
d C5b-9 to activate JAK1 and STAT3 proteins, thus defining new signalling p
athway by which C5b-9 may regulate gene activation. (C) 1999 Elsevier Scien
ce B.V. All rights reserved.