Role of nonreceptor protein tyrosine kinases during phospholipase C-gamma 1-related uterine contractions in the rat.
Activated phospholipase C1, produced in response to tyrosine phosphorylation, appears to play an important role during uterine contractions. These studies sought to determine which non-receptor protein tyrosine kinases are involved in the activation of phospholipase C1 in rat uterine tissue. In vitro contraction studies were performed utilizing isoform specific protein tyrosine kinase inhibitors. Western blots were performed utilizing antibodies to phosphotyrosine-phospholipase C1, total phospholipase C1, c-Src kinase and Lck kinase. Spontaneous, stretch-stimulated, and bpV(phen) (tyrosine phosphatase inhibitor) enhanced uterine contractions were significantly suppressed in response to Damnacanthal (Lck kinase inhibitor) and PP1 (c-Src kinase inhibitor). Damnacanthal and PP1 also significantly suppressed bpV(phen)-enhanced tyrosine phosphorylation of phospholipase C1. Western blots confirmed expression of Lck kinase and c-Src kinase in uterine tissue. In conclusion, the Lck and c-Src kinases appear to play an important role in regulating tyrosine phosphorylation of phospholipase C1 and contractile activity in the rat uterus.
Phillippe
Mark
M
Department of Obstetrics, Gynecology and Reproductive Sciences, University of Vermont College of Medicine, Burlington, Vermont 05405, USA. Mark.Phillippe@uvm.edu
Sweet
Leigh M
LM
Bradley
Diana F
DF
Engle
Daniel
D
D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology; D015153:Blotting, Western; D005260:Female; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009942:Organometallic Compounds / Q000494:pharmacology; D010618:Phenanthrolines / Q000494:pharmacology; D051966:Phospholipase C gamma / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013267:Stilbenes / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors; D014590:Uterine Contraction / Q000187:drug effects; D014599:Uterus / Q000187:drug effects / Q000201:enzymology*
C108123:4-amino-5-(4-methylphenyl)-7-(tert-butyl)pyrazolo(3,4-d)pyrimidine; D000880:Anthraquinones; D007211:Indoles; D009942:Organometallic Compounds; D010618:Phenanthrolines; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C416927:SU 6656; D013267:Stilbenes; D013449:Sulfonamides; D019000:Phosphotyrosine; C079170:damnacanthal; C102120:bisperoxo(1,10-phenanthroline)oxovanadate(1-); C041525:3,3',4,5'-tetrahydroxystilbene; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D016392:Proto-Oncogene Proteins pp60(c-src); D017027:Protein Tyrosine Phosphatases; D051966:Phospholipase C gamma