Enzyme regulating ether lipid signaling pathways

US8940497B2 · kind B2 · utility

Assignee

• THE SCRIPPS RESEARCH INSTITUTE · US

Inventors

• Benjamin F. Cravatt · San Diego, US
• Kyle P. Chiang · Irvine, US
• Sherry Niessen · San Diego, US
• Alan Saghatelian · San Diego, US

Key dates

• Filing date: Aug 14, 2012
• Grant date: Jan 27, 2015
• Expiry date: Apr 4, 2033

Classification

• Technology area (CPC G): Physics
• CPC primary: G01N2500/02
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

A multidimensional profiling strategy that combines activity-based proteomics and metabolomics was used to determine that an active protein, which is a previously uncharacterized enzyme highly elevated in aggressive cancer cells, serves as a central node in an ether lipid signaling network that bridges platelet-activating factor and the lysophospholipids. Biochemical studies confirmed that the active protein regulates this pathway by hydrolyzing the metabolic intermediate 2-acetyl monoalkylglycerol. Inactivation of the active protein disrupted ether lipid metabolism in cancer cells and impaired cell migration and tumor growth in vivo.