Role of Non-receptor Protein Tyrosine Kinases During Phospholipase C-γ1 Related Uterine Contractions in the Rat

Activated phospholipase Cγ1 (PLC-γ1), 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 (PTKs) are involved in the tyrosine phosphorylation and activation of PLC-γ1 in uterine tissue from the rat. In vitro uterine contraction studies were performed utilizing isoform specific PTK inhibitors. Western blots were performed utilizing antibodies to phosphotyrosine-PLC-γ1, total PLC-γ1, c-Src kinase and Lck kinase. Spontaneous, stretch-stimulated, and bpV(phen) (a tyrosine phosphatase inhibitor) enhanced uterine contractions were significantly suppressed in response to Damnacanthal (a Lck kinase inhibitor) and PP1 (a c-Src kinase inhibitor); whereas, several other PTK isoform inhibitors had no significant effect. Damnacanthal and PP1 also significantly suppressed bpV(phen)-enhanced tyrosine phosphorylation of PLC-γ1 compared to other PTK isoform inhibitors. Western blots confirmed expression of the Lck and c-Src kinases in uterine tissue. In conclusion, the Lck and c-Src kinases appear to play an important role in regulating tyrosine phosphorylation of PLC-γ1 and contractile activity in the rat uterus.