Different elements of mini-helix 1 are required for human growth hormone or prolactin action via the prolactin receptor.
Human growth hormone (hGH) and prolactin (hPRL) have a low sequence homology, but both bind and activate hPRL receptors. hGH also binds hGH receptors. hGH has 22 and 20 kDa forms; residues 32-46 have been deleted by alternative RNA splicing to create the smaller form. hGH requires F44 for activity through the hPRL receptor, but not for activity through the hGH receptor. The deletion of F44 from hGH has the same effect as removal of residues 32-46 (approximately 200-fold loss in activity), indicating the importance of F44 in hGH when activating the hPRL receptor. In contrast, when the homologous F50 is deleted from hPRL little or no activity is lost, indicating that this highly conserved phenylalanine is not required for the action of hPRL. Deletion of residues 41-52 (a non-conserved sequence homologous to residues 32-46 of hGH) reduced the activity of hPRL by >14 000-fold. This region is essential for the biological activity of hPRL. As these two proteins have evolved from a common ancestor, they have retained the requirement for this region but need different structural elements to activate hPRL receptors. Such diversity represents an opportunity to fine-tune hormone activity.
Peterson
F C
FC
The Ohio State Biochemistry Program, Department of Veterinary Biosciences, The Ohio State University, 1925 Coffey Road, Columbus 43210, USA.
Brooks
C L
CL
D000595:Amino Acid Sequence; D001681:Biological Assay; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D019382:Human Growth Hormone / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D011388:Prolactin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D011981:Receptors, Prolactin / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship
D011981:Receptors, Prolactin; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D011388:Prolactin