- Phospholipase C and inositol lipid signaling
- P2Y receptors for extracellular nucleotides
- G proteins
The physiological responses of many hormones, neurotransmitters, growth factors, and other extracellular stimuli are mediated through phospholipase C (PLC)-catalyzed hydrolysis of membrane phosphoinositides. A long-term goal of our research is to delineate the molecular mechanisms whereby PLC activity is modulated by receptor-activated heterotrimeric and Ras superfamily G proteins, as well as by tyrosine phosphorylation. This work focuses on three PLC isozymes: (1) PLC-β isozymes, which are the prototypical heterotrimeric G protein-regulated PLCs, (2) PLC-ε, which is uniquely directly activated by both Rho and Ras GTPases acting through independent domains, and (3) PLC-γ isozymes, which are activated by phosphorylation by receptor and non-receptor tyrosine kinases.
Our research also focuses on mechanistic and pharmacological aspects of a class of G protein-coupled receptors (the eight member P2Y receptor family) that are activated by extracellular nucleotides.