Medical College of Wisconsin
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Different elements of mini-helix 1 are required for human growth hormone or prolactin action via the prolactin receptor. Protein Eng Des Sel 2004 May;17(5):417-24 PMID: 15252206

Abstract

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.

Author List

Peterson FC, Brooks CL

Author

Francis C. Peterson PhD Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amino Acid Sequence
Biological Assay
Dose-Response Relationship, Drug
Electrophoresis, Polyacrylamide Gel
Human Growth Hormone
Humans
Molecular Sequence Data
Prolactin
Protein Structure, Tertiary
Receptors, Prolactin
Recombinant Proteins
Spectrometry, Fluorescence
Structure-Activity Relationship



View this publication's entry at the Pubmed website PMID: 15252206
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