Arachidonate and Related Unsaturated Fatty Acids Selectively Inactivate the Guanine Nucleotide-binding Regulatory Protein, Gzα

• DOI: 10.1074/jbc.271.6.2949
• Publication Date: 2002-07-26T15:15:23Z
• Authors: Jennifer Glick; Gabriela Santoyo; Patrick J. Casey
• Keywords: 0303 health sciences; Arachidonic Acid; Fatty Acids, Nonesterified; Guanosine Diphosphate; Recombinant Proteins; Kinetics; 03 medical and health sciences; GTP-Binding Proteins; Guanosine 5'-O-(3-Thiotriphosphate); Escherichia coli; Animals; Cloning, Molecular; Micelles; Signal Transduction

Gz is a member of the family trimeric guanine nucleotide-binding regulatory proteins (G proteins), which plays crucial role in signaling across cell membranes. The expression predominately confined to neuronal cells and platelets, suggesting an involvement neuroendocrine process. Although pathway participates not yet known, it has been linked inhibition adenylyl cyclase. We have found that arachidonate related unsaturated fatty acids suppress nucleotide binding α subunit Gz. This by cis-unsaturated specific for Gzα; other G protein subunits are relatively insensitive these lipids. IC50 lipids closely corresponds their critical micellar concentrations, interaction lipid micelle with Gzα primary event leading inhibition. presence acidic group acid inhibition, as no effect observed corresponding alcohol. While arachidonic produces near-complete both GDP guanosine 5′-(3-O-thio)triphosphate Gzα, release from was unaffected. Furthermore, rate inactivation essentially identical protein, indicating required inactivation. These observations indicate mechanism through nucleotide-free form protein. physiologic significance this finding unclear, similar effects on involved potential roles signal modulation. Additionally, ability inactivate cyclase-inhibitory provides molecular previous findings treatment platelets results elevated cAMP levels.