Down-regulation of increased signal transductioncapacity in human cancer cells

摘要

The discovery of the stringent linkage with malignancy of elevated signaltransduction activity and IP3 (inositol 1,4,5-trisphosphate) concentration in themembrane reveals novel targets for rationally designed clinical chemotherapy(Weber et al., 2000). In what may be called the business-end of signal transduction,phosphatidylinositol (PI) is converted to 1-phosphatidylinositol-4-phosphate (PIP)and then to PIP2 (PI 4,5-bisphosphate) through the actions of PI 4-kinase (EC2.7.1.67) and PIP kinase (PI 4-phosphate-5-kinase, EC 2.7.1.68) (Fig. 1). PIP2 can bemetabolized by phospholipase C (1-PIP2 phosphodiesterase, EC 3.1.4.11) forsynthesis of IP3 and DAG (diacylglycerol). Increased IP3 concentration leads tothe release of calcium from intracellular sources and DAG activates protein kinaseC. Thus, this signal transduction cascade involving PI, PIP, PIP2 and 1P3 forms aphosphorylation pathway through the action of PI and PIP kinases and thephosphodiesterase action of PLC.