Jump to main content
United States Environmental Protection Agency
Laws & Regulations
Health & Environmental Research Online (HERO)
Export to File
This record has one attached file:
Add More Files
Display Name for File*:
Profilin and gelsolin stimulate phosphatidylinositol 3-kinase activity
Chauhan, VPS; Singh, S; Murakami, N; Chauhan, A
Is Peer Reviewed?
Phosphoinositides bind to several cytoskeletal proteins including profilin and gelsolin, and regulate their functions. It has been reported that profilin inhibits the phospholipase C -dependent hydrolysis of phosphatidylinositol (PI) 4,5-bisphosphate (PIP2]. We report here that both profilin and gelsolin stimulate 3-OH phosphorylation of PIP2 by PI 3-kinase (PI 3-K) in a concentration-dependent manner. This effect was specific as other cytoskeletal proteins such as tau or actin did not affect PI 3-K activity. PI 3-K stimulation was observed at all the PIP2 concentrations studied. Kinetic analysis showed that profilin affects the Vmax of the enzyme. Profilin binds to phosphoinositides in the order of PIP2 > PIP >>PI. When mixture of phosphoinositides i.e. PI, PIP and PIP2 was used, profilin stimulated phosphorylation of all three phosphoinositides. Since PI 3-K-dependent phosphorylation of PI (which has little or no affinity for profilin) was also stimulated by profilin, it suggested that there may be direct interaction of PI 3-K and profilin. Dot-Blot analysis using antibody to p85 subunit of PI 3-K confirmed that p85 binds to profilin. PI 3-K has dual activity as it phosphorylates lipids (phosphoinositides) and proteins (p85 subunit of PI 3-K). The binding of profilin to PI 3-K did not have any effect on the protein kinase activity of the enzyme. PI 3-K also did not affect the actin sequestering ability of profilin (determined by pyrene-labelled actin) suggesting that actin and p85 bind to profilin at different sites. These studies suggest that profilin and gelsolin may regulate the generation of 3-OH phosphorylated phosphoinositides.
Learn about HERO
Projects in HERO
Transparency & Integrity