Platelet-Derived Growth Factor Increases the In Vivo Activity of Phospholipase C-γ₁ and Phospholipase C-γ₂

Abstract

Upon binding to its cell surface receptor, platelet-derived growth factor (PDGF) causes the tyrosine phosphorylation of phospholipase C-γ₁ (PLC-γ₁ and stimulates the production of diacylglycerol and inositol 1,4,5-triphosphate. We showed that following stimulation by PDGF, rat-2 cells overexpressing PLC-γ₁ display an increase in the levels of both tyrosine-phosphorylated PLC-γ₁ and inositol phosphates compared with the parental rat-2 cells. This increased responsiveness to PDGF is a direct effect of PLC-γ₁ overexpression, as a cell line expressing similar levels of an enzymatically inactive point mutant of PLC-γ₁, PLC-γ₁335Q, did not show elevated inositol phosphate production in response to PDGF. Hematopoietic cells express PLC-γ₁, a PLC isoform that is closely related to PLC-γ₁. When rat-2 cells overexpressing PLC-γ₂ were treated with PDGF, an increase in both the tyrosine phosphorylation and the in vivo activity of PLC-γ₂ was observed. Aluminum fluoride (AIF₄^-), a universal activator of PLC linked to G-proteins, did not produce an increase in the levels of inositol phosphates in either of the overexpressing cell lines compared with parental rat-2 cells, demonstrating that PLC-γ isoforms respond specifically to a receptor with tyrosine kinase activity.