"Our wildest speculation says SF-1 may have been one of the first primordial receptors, and that it received signals via phosphorylation signals, not via ligands. When the AF-1 domain was moved down to the other end of the molecule in these receptors, then the need for ligands may have been more pressing." The researchers' next step is to try to determine at a structure level if this ligand-binding domain is reconfigured, bypassing the need for a ligand.
"Phosphorylation might well be the principal method of modulation of this orphan receptor," said Ingraham, "though we still cannot exclude the possibility that SF-1 activity depends on a ubiquitous ligand present in most cell types."
Other co-authors of the study were Irina Krylova, of the Department of Physiology at UCSF; Yixian Zhang, of the Department of Cell Biology at Baylor College of Medicine; Beatrice D. Darimont, PhD, postdoctoral fellow of the Department of Cellular and Molecular Pharmacology at UCSF; Kimberly Simpson, a UCSF Summer Student and Nancy L. Weigel, PhD, associate professor of the Department of Cell Biology at Baylor College of Medicine. The study was funded by the National Institutes of Health.