• Home
  • Search Results
  • Phosphatidylinositol 5 Phosphate 4-Kinase Regulates Plasma-Membrane PIP3 Turnover and Insulin Signaling.

Phosphatidylinositol 5 Phosphate 4-Kinase Regulates Plasma-Membrane PIP3 Turnover and Insulin Signaling.

Cell reports (2019-05-16)
Sanjeev Sharma, Swarna Mathre, Visvanathan Ramya, Dhananjay Shinde, Padinjat Raghu
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 required for normal growth and metabolism. We report that in Drosophila, phosphatidylinositol 5 phosphate 4-kinase (PIP4K) is required to limit PIP3 levels during insulin receptor activation. Depletion of PIP4K increases the levels of PIP3 produced in response to insulin stimulation. We find that PIP4K function at the plasma membrane enhances class I phosphoinositide 3-kinase (PI3K) activity, although the catalytic ability of PIP4K to produce phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] at the plasma membrane is dispensable for this regulation. Animals lacking PIP4K show enhanced insulin signaling-dependent phenotypes and are resistant to the metabolic consequences of a high-sugar diet, highlighting the importance of PIP4K in normal metabolism and development. Thus, PIP4Ks are key regulators of receptor tyrosine kinase signaling with implications for growth factor-dependent processes including tumor growth, T cell activation, and metabolism.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Insulin from bovine pancreas, powder, BioReagent, suitable for cell culture
Sigma-Aldrich
Anti-Actin (20-33) antibody produced in rabbit, IgG fraction of antiserum, buffered aqueous solution
Avanti
17:0-20:4 PI(3,4,5)P3, 1-heptadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phospho-(1′-myo-inositol-3′,4′,5′-trisphosphate) (ammonium salt), powder
Avanti
17:0-20:4 PI(3,4)P2, 1-heptadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phospho-(1′-myo-inositol-3′,4′-bisphosphate) (ammonium salt), powder