Biology

Dr. Raghu Padinjat
National Centre for Biological Sciences, Bangalore.

Abstract:

Phosphatidylinositol-3,4,5-trisphosphate (PIP₃) generation at the plasma membrane is a key event during activation of receptor tyrosine kinases such as the insulin receptor and is critical for normal growth and metabolism. The lipid kinases and phosphatases regulating PIP₃ levels are described but mechanisms that control their activity remains unclear. I will discuss our recent work on the regulation of PIP₃ levels during insulin receptor activation by phosphatidylinositol 5 phosphate 4-kinase (PIP4K). Depletion of PIP4K increases PIP₃ levels and augments sensitivity to insulin through enhanced Class I phosphoinositide 3-kinase (PI3K) activity. Plasma membrane localized PIP4K was sufficient to control PIP₃ levels. Animals lacking PIP4K show enhanced insulin dependent phenotypes in vivo and resistance to the metabolic consequences of a high-sugar diet. Thus, PIP4K is required for normal metabolism and development. These findings define PIP4Ks as regulators of receptor tyrosine kinase signalling with implications for growth factor dependent processes including tumour growth, T-cell activation and metabolism.