Role of B61, the ligand for the Eck receptor tyrosine kinase, in TNF-alpha-induced angiogenesis.
B61, a cytokine-inducible endothelial gene product, is the ligand for the Eck receptor protein tyrosine kinase (RPTK). Expression of a B61-immunoglobulin chimera showed that B61 could act as an angiogenic factor in vivo and a chemoattractant for endothelial cells in vitro. The Eck RPTK was activated by tumor necrosis factor-alpha (TNF-alpha) through induction of B61, and an antibody to B61 attenuated angiogenesis induced by TNF-alpha but not by basic fibroblast growth factor. This finding suggests the existence of an autocrine or paracrine loop involving activation of the Eck RPTK by its inducible ligand B61 after an inflammatory stimulus, the net effect of which would be to promote angiogenesis, a hallmark of chronic inflammation.
Pandey
A
A
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109, USA.
Shao
H
H
Marks
R M
RM
Polverini
P J
PJ
Dixit
V M
VM
D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002478:Cells, Cultured; D002633:Chemotaxis; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D004789:Enzyme Activation; D036382:Ephrin-A1; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009389:Neovascularization, Pathologic / Q000209:etiology*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011506:Proteins / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D036104:Receptor, EphA2; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D036382:Ephrin-A1; D008565:Membrane Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D011505:Protein-Tyrosine Kinases; D036104:Receptor, EphA2