Faculty Collaboration Database

Identification of a motif associated with the lactogenic actions of human growth hormone. J Biol Chem 1997 Aug 22;272(34):21444-8

Date

08/22/1997

Pubmed ID

9261160

DOI

10.1074/jbc.272.34.21444

Scopus ID

2-s2.0-0030881666 (requires institutional sign-in at Scopus site)   15 Citations

Abstract

Human growth hormone (hGH) stimulates somatogenic and lactogenic actions through the GH and prolactin (PRL) receptors, respectively. In contrast, non-primate GHs stimulate only somatotropic action. Phe44, of the human GH sequence is present in all hormones stimulating lactogenic action and absent in all hormones stimulating only somatotropic action. We speculate that the presence of Phe44 is a feature necessary for specifying lactogenic activity. In this report, the role of Phe44 was investigated by its deletion or substitution with alanine or leucine. Deletion of Phe44 or substitution with leucine did not significantly change the structure of hGH as determined by circular dichroism, absorbance, and fluorescence spectroscopies. In contrast, substitution of alanine perturbed the structure. Deletion of Phe44 reduced binding affinity for the lactogenic receptor, resulting in a reduced activation. Substitution with either alanine or leucine partially restored lactogenic receptor binding affinity, which correlated with the hormones' activity in the Nb2 rat lymphoma cells. All the recombinant hGHs had similar somatotropic activities in FDC-P1 cells transfected with the hGH receptor. These data indicate that the hydrophobic side chain of Phe44 is required for lactogenic receptor binding and activation but is unnecessary for somatotropic action.

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

Alanine
Animals
Biological Assay
Circular Dichroism
Cloning, Molecular
Growth Hormone
Humans
Lactation
Leucine
Phenylalanine
Protein Structure, Secondary
Rats
Receptors, Prolactin
Receptors, Somatotropin
Recombinant Proteins
Spectrometry, Fluorescence
Spectrophotometry, Ultraviolet
Structure-Activity Relationship