The role of the WSXWS equivalent motif in growth hormone receptor function

Baumgartner, J. W., Wells, C. A., Chen, C. -M. and Waters, M. J. (1994) The role of the WSXWS equivalent motif in growth hormone receptor function. Journal of Biological Chemistry, 269 46: 29094-29101.

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Author Baumgartner, J. W.
Wells, C. A.
Chen, C. -M.
Waters, M. J.
Title The role of the WSXWS equivalent motif in growth hormone receptor function
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
Publication date 1994-11
Sub-type Article (original research)
Open Access Status File (Publisher version)
Volume 269
Issue 46
Start page 29094
End page 29101
Total pages 8
Place of publication Bethesda, MD, United States
Publisher American Society for Biochemistry and Molecular Biology
Language eng
Formatted abstract
Members of the cytokine receptor family have a consensus WSXWS sequence (WS motif) in the extracellular domain. With the interleukin-2, erythropoietin, and prolactin receptors, alteration of the WS sequence disrupts ligand binding and receptor signaling. The structural basis for these effects is unclear. To examine the role of the WS equivalent sequence (Y222GEFS226) in the function of the growth hormone receptor, each residue was mutated to alanine or to the WS consensus sequence. Although we used stable cell lines expressing all of these mutants, we show only three mutants, Y222A, G223A, and S226A, which display lower ligand affinity. Using conformation-specific monoclonal antibodies, we show that Y222A and S226A receptors have structural perturbations, which result in decreased signal transduction. This was shown by a decreased ability of growth hormone to stimulate protein synthesis and to transactivate the c-fos promoter with these mutants. The crystal structure of the ligand-occupied extracellular domain of growth hormone receptor indicates that Tyr222 and Ser226 have important interactions within the second β-barrel domain, providing a structural basis for our results. The WS segment is not involved in sequence- specific accessory protein interaction, as mutation of residues Gly223, Glu224, and Phe225 does not alter receptor function.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Australian Institute for Bioengineering and Nanotechnology Publications
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Created: Wed, 09 Mar 2011, 14:32:34 EST