Editors' ChoiceStructural Biology

The Hormone’s Message

Science Signaling  20 May 2014:
Vol. 7, Issue 326, pp. ec134
DOI: 10.1126/scisignal.2005489

The receptor for growth hormone is a well-studied representative of a family of cytokine receptors through which binding of hormone molecules at the cell surface is converted into a biochemical signal within the cell. Brooks et al. (see the Perspective by Wells and Kossiakoff) used a combination of crystal structures, biophysical measurements, cell biology experiments with modified receptors, and molecular dynamics and modeling to decipher how the receptor actually transmits the information that a hormone molecule is bound. The results suggest that the receptors exist in inactive dimeric complexes in which two associated JAK2 protein kinase molecules interact in an inhibitory manner. Binding of growth hormone causes a structural change in the receptor that results in movement of the receptor intracellular domains apart from one another. This relieves the inhibition of the JAK2 molecules and allows them to activate one another, thus initiating the cellular response to the hormone.

A. J. Brooks, W. Dai, M. L. O’Mara, D. Abankwa, Y. Chhabra, R. A. Pelekanos, O. Gardon, K. A. Tunny, K. M. Blucher, C. J. Morton, M. W. Parker, E. Sierecki, Y. Gambin, G. A. Gomez, K. Alexandrov, I. A. Wilson, M. Doxastakis, A. E. Mark, M. J. Waters, Mechanism of activation of protein kinase JAK2 by the growth hormone receptor. Science 344, 1249783 (2014). [Abstract] [Full Text]

J. A. Wells, A. A. Kossiakoff, New tricks for an old dimer. Science 344, 703–704 (2014). [Summary] [Full Text]

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