Skip Navigation



PEDS Advance Access published online on July 13, 2004
Protein Engineering Design and Selection, doi:10.1093/protein/gzh051
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
17/5/417    most recent
gzh051v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Peterson, F. C.
Right arrow Articles by Brooks, C. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Peterson, F. C.
Right arrow Articles by Brooks, C. L.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Received February 12, 2004
Revised April 29, 2004
Accepted May 21, 2004

Article

Different elements of mini-helix 1 are required for human growth hormone or prolactin action via the prolactin receptor

F. C. Peterson 1 C. L. Brooks 2*

1 The Ohio State Biochemistry Program, The Ohio State University, 1925 Coffey Road, Columbus, Ohio 43210, US
2 The Ohio State Biochemistry Program, The Ohio State University, 1925 Coffey Road, Columbus, Ohio 43210, US; Department of Veterinary Biosciences, The Ohio State University, 1925 Coffey Road, Columbus, Ohio 43210, US; Department of Biochemistry, The Ohio State University, 1925 Coffey Road, Columbus, Ohio 43210, US

* To whom correspondence should be addressed. E-mail: Brooks.8{at}osu.edu.


  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 through 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 through 46 (approximately a 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 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 greater than 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.

Keywords: prolactin; growth hormone; human; rat.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
Z. Papper, N. M. Jameson, R. Romero, A. L. Weckle, P. Mittal, K. Benirschke, J. Santolaya-Forgas, M. Uddin, D. Haig, M. Goodman, et al.
Ancient origin of placental expression in the growth hormone genes of anthropoid primates
PNAS, October 6, 2009; 106(40): 17083 - 17088.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L. A. Svensson, K. Bondensgaard, L. Norskov-Lauritsen, L. Christensen, P. Becker, M. D. Andersen, M. J. Maltesen, K. D. Rand, and J. Breinholt
Crystal Structure of a Prolactin Receptor Antagonist Bound to the Extracellular Domain of the Prolactin Receptor
J. Biol. Chem., July 4, 2008; 283(27): 19085 - 19094.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
N. Polgar, B. Fogelgren, J. M. Shipley, and K. Csiszar
Lysyl Oxidase Interacts with Hormone Placental Lactogen and Synergistically Promotes Breast Epithelial Cell Proliferation and Migration
J. Biol. Chem., February 2, 2007; 282(5): 3262 - 3272.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.