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Direct Activation of Epac by Sulfonylurea Is Isoform Selective by Katie J. Herbst; Carla Coltharp; L. Mario Amzel; Jin Zhang is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is Direct Activation of Epac by Sulfonylurea Is Isoform Selective about?

Commonly used as a treatment for Type II diabetes, sulfonylureas (SUs) stimulate insulin secretion from pancreatic b cells by binding to sulfonylurea receptors. Recently, SUs have been shown to also activate exchange protein directly activated by cAMP 2 (Epac2), however, little is known about this molecular action. Using biosensor imaging and biochemical analysis, we show that SUs activate Epac2 and the downstream signaling via direct binding to Epac2. We further identify R447 of Epac2 to be critically involved in SU binding. This distinct binding site from cAMP points to a new mode of allosteric activation of Epac2. We also show that SUs selectively activate Epac2 isoform, but not the closely related Epac1, further establishing SUs as a new class of isoform-selective enzyme activators.

Who reads Direct Activation of Epac by Sulfonylurea Is Isoform Selective?

Author

Katie J. Herbst; Carla Coltharp; L. Mario Amzel; Jin Zhang

Publisher

Elsevier Science; Elsevier ; Cell Press; Elsevier BV (ISSN 1074-5521)

Published

2011

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)