Phosphatidylinositol 5 phosphate 4-kinase regulates plasma-membrane pip3 turnover and insulin signaling

Swarna, Mathre (2019) Phosphatidylinositol 5 phosphate 4-kinase regulates plasma-membrane pip3 turnover and insulin signaling. Cell Reports, 27 (7). pp. 1-37. ISSN 2211-1247

[img] PDF
2 -Phosphatidylinositol 5 Phosphate 4-Kinase Regulates PlasmaMembrane PIP3 Turnover and Insulin Signaling.pdf - Published Version
Restricted to Registered users only

Download (2MB) | Request a copy

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.

Item Type: Article
Subjects: Research > Research Center - Health Sciences
Depositing User: KMC Library
Date Deposited: 01 Jul 2020 06:51
Last Modified: 01 Jul 2020 06:51
URI: http://eprints.manipal.edu/id/eprint/155033

Actions (login required)

View Item View Item