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Minireview: Receptor Dimerization in GH and Erythropoietin Action—It Takes Two to Tango, But How?

Department of Medicine, Division of Endocrinology and Metabolism, and Departments of Cell Biology and Physiology, University of Alabama at Birmingham, and Veterans Affairs Medical Center, Birmingham, Alabama 35294

Address all correspondence and requests for reprints to: Stuart J. Frank, University of Alabama at Birmingham, 1530 Third Avenue South, BDB 861, Birmingham, Alabama 35294-0012. E-mail: frank{at}endo.dom.uab.edu

The receptors for GH and erythropoietin are members of the cytokine receptor superfamily. They are single membrane-spanning proteins that bind ligand in the extracellular domain and couple to cytosolic JAK tyrosine kinases to initiate signaling. The ligand-engaged GH receptor (GHR) and erythropoietin receptor (EpoR) extracellular domains are believed to exist in a dimerized configuration in which a single ligand molecule engages two receptor extracellular domains. The last several years have witnessed a rapid expansion in our knowledge of the structural and functional details of this dimerization process and have forced a reexamination of how the ligand-containing complexes achieve their conformation. For EpoR, there is good evidence that the unliganded receptor is already a preformed dimer that is activated by a ligand-induced change in the receptor conformation. Owing in some measure to the unavailability of the analogous crystal structure of the unliganded GHR extracellular domain, it is still unknown whether GHR adopts a similar preformed dimer/conformational change in response to GH as is found for EpoR. This review critically examines the state of our knowledge pertaining to GHR and EpoR dimerization, noting differences and similarities between the two.

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