Poster abstracts

Poster number 49 submitted by Wei Liu

Structural basis for ligand-independent dimerization of human prolactin receptor

Wei Liu (OSBP, Department of Veterinary Biosciences, The Ohio State University), Charles Brooks (Department of Veterinary Biosciences, The Ohio State University)

Abstract:
The human prolactin receptor (hPRLr) has been recently reported to form inert ligand-independent dimers on plasma membrane. This discovery challenges the classic model of hPRLr activation which shows that ligand binding induces receptor dimerization and that the proximity of the dimeric receptors triggers activation. However, little work has been done to determine the structural elements in hPRLr that mediate ligand-independent dimerization. This work investigates the role of disulfide linkage in hPRLr ligand-independent dimerization using reducing and non-reducing SDS-PAGE. Treatment with ionic and non-ionic reducing reagents on hPRLr on plasma membrane is used to dissect which cystein residues in hPRLr are involved in forming disulfide linkage. Non-covalent interactions between the transmembrane (TM) domains of ligand-independent dimers are also being examined using FRET technique.

References:
Brown RJ, Waters MJ, et al. Nat Struct Mol Biol 12: 814-821 (2005)
Constantinescu SN, Lodish HF, et al. PNAS 98: 4379-4384 (2001)
Gadd SL, Clevenger CV. Mol Endocrinol 20: 2734-2746 (2006)
Otterman KM, Koshland DE, et al. Science 285: 1751-1754 (1999)
Quazi AM, Dufau ML, et al. Mol Endocrinol 20: 1912-1923 (2006)
Remy I, Michick SW, et al. Science 283: 990-993 (1999)

Keywords: prolactin receptor, disulfide linkage, FRET