Volume 90 Issue 44 | p. 20 | Concentrates
Issue Date: October 29, 2012

How Leptin Starts Signaling

Electron microscopy data reveal how metabolism-regulating hormone interacts with its receptor
Department: Science & Technology
News Channels: Biological SCENE, Analytical SCENE
Keywords: leptin, obesity, Jak kinase, cancer, structural biology, electron microscopy
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This cartoon depicts how two copies of leptin (red, orange) lock two copies of the leptin receptor (dark green, aqua) in place, triggering signaling by Janus kinase (green).
Credit: Adapted from Mol. Cell
This cartoon depicts how two copies of leptin (red, orange) lock two copies of the leptin receptor (dark green, aqua) into place, triggering signaling by Jak kinase (green).
 
This cartoon depicts how two copies of leptin (red, orange) lock two copies of the leptin receptor (dark green, aqua) in place, triggering signaling by Janus kinase (green).
Credit: Adapted from Mol. Cell

Using electron microscopy, researchers have amassed new insights about how the hormone leptin interacts with its receptor (Mol. Cell, DOI: 10.1016/j.molcel.2012.09.003). Signals from leptin, which is secreted by fat tissue, affect metabolism. This biochemical pathway has intrigued obesity drug researchers for more than a decade. But the arrangement of leptin’s signaling complex is in dispute, with camps proposing either a 2:2 or a 2:4 ratio of leptin to its receptor. Georgios Skiniotis and colleagues at the University of Michigan now provide strong evidence that the ratio is 2:2. They observed two copies of leptin that engaged two copies of the rod-shaped receptor, locking the floppy rods into place. They propose that this locking mechanism is key for signaling. The next step, Skiniotis says, will be to determine a structure of the complex that includes Janus kinase, an enzyme that mediates leptin signaling and is itself a drug target for cancer and immune disorders. Skiniotis adds that the mechanism of leptin signaling parallels that of related proteins, such as interleukin-6, which is implicated in cancer.

 
Chemical & Engineering News
ISSN 0009-2347
Copyright © American Chemical Society

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