Endothelin-1 induces tyrosine phosphorylation in human blood monocytes.
Mediators including the neuropeptide endothelin-1 (ET-1), which are released in response to injury, modulate the expression of cell adhesion molecules on leukocytes and endothelial cells. The mechanisms underlying this process are not clear. In this study we investigated the effect of endothelin-1 on the expression of tyrosine phosphorylated proteins in human blood monocytes. Endothelin-1 caused an increase in tyrosine phosphorylated proteins in monocytes in a time-dependent and dose-dependent manner, the Mr 60, 80 and 110 kDa proteins being the most prominent. This effect was blocked by pre-incubating the monocytes with the selective tyrosine kinase inhibitors genistein or herbimycin A. Endothelin-1 induced upregulation of tyrosine phosphorylated proteins appears to be mediated by the ETA receptor. Unlike our previously reported studies in endothelial cells, immunoprecipitation with anti-src or anti-JAK antibodies followed by immunoblotting with PY20 in human blood monocytes revealed that these proteins of Mr 60, 80 and 110 kDa were not related to src or JAK kinases. These findings suggest that ET- exerts its effect on monocytes by a pathway involving tyrosine kinases other than src or JAK kinases.
Chisholm
L J
LJ
Department of Surgery, Creighton University School of Medicine, Omaha, Nebraska 68131, USA.
Agrawal
D K
DK
Pearson
T J
TJ
Edwards
J D
JD
D000328:Adult; D019138:Antibodies, Blocking / Q000276:immunology; D016227:Benzoquinones; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D005260:Female; D019833:Genistein; D006801:Humans; D066298:In Vitro Techniques; D007529:Isoflavones / Q000494:pharmacology; D053613:Janus Kinase 1; D047029:Lactams, Macrocyclic; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000032:analysis / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology; D011506:Proteins / Q000378:metabolism*; D011809:Quinones / Q000494:pharmacology; D017466:Receptors, Endothelin / Q000502:physiology; D017828:Rifabutin / Q000031:analogs & derivatives; D013997:Time Factors; D014443:Tyrosine / Q000378:metabolism*; D019061:src-Family Kinases / Q000032:analysis / Q000276:immunology
D019138:Antibodies, Blocking; D016227:Benzoquinones; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D007529:Isoflavones; D047029:Lactams, Macrocyclic; D011506:Proteins; D011809:Quinones; D017466:Receptors, Endothelin; D017828:Rifabutin; D014443:Tyrosine; C020754:herbimycin; D019833:Genistein; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; D053613:Janus Kinase 1; D019061:src-Family Kinases