Ligand-specific dimerization of the extracellular domain of the bovine growth hormone receptor.
The bovine growth hormone (bGH) receptor and its extracellular domain (bGHBP) bind two protein hormones with high affinity; bGH and bovine placental lactogen (bPL). However, each of these hormones bind with a different stoichiometry. bGH binds to the bGHBP in a 1:2 ratio while bPL binds in a 1:1 ratio. Scatchard analysis of saturation binding yields similar apparent dissociation constants (Kd) for bGH and bPL of 1.4 x 10(-11) M and 3.0 x 10(-11) M, respectively, for the membrane receptor and 6.8 x 10(-11) M and 4.2 x 10(-11) M, respectively, for bGHBP. In competition experiments using either liver membranes or bGHBP, bGH is 2-3-fold more effective than bPL in competing for 125I-bGH-binding sites. In similar experiments using 125I-bPL, bPL is 50-fold more effective than bGH in competing for binding sites. A rat monoclonal antibody raised against bGHBP competes effectively for 125I-bGH-binding sites, but not for 125I-bPL-binding sites. Since bPL cannot dimerize the bGHBP and yet it acts in part as a somatogen in vivo, homodimerization of the growth hormone receptor is apparently not essential for some biological responses signaled through this receptor.
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Monsanto Corporate Research, Monsanto Company, Chesterfield, Missouri 63198.
Byatt
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D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001665:Binding Sites; D001667:Binding, Competitive; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D013006:Growth Hormone / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D007457:Iodine Radioisotopes; D046911:Macromolecular Substances; D008862:Microsomes, Liver / Q000648:ultrastructure; D008969:Molecular Sequence Data; D010928:Placental Lactogen / Q000378:metabolism*; D011247:Pregnancy; D011986:Receptors, Somatotropin / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry
D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D046911:Macromolecular Substances; D011986:Receptors, Somatotropin; D011994:Recombinant Proteins; D013006:Growth Hormone; D010928:Placental Lactogen