JBC Origene Your Gene Company

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
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 Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Diamond, S. E.
Right arrow Articles by Gutierrez-Hartmann, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Diamond, S. E.
Right arrow Articles by Gutierrez-Hartmann, A.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Volume 271, Number 46, Issue of November 15, 1996 pp. 28925-28932
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

A 26-Amino Acid Insertion Domain Defines a Functional Transcription Switch Motif in Pit-1beta

(Received for publication, June 12, 1996, and in revised form, August 5, 1996)

Scott E. Diamond and Arthur Gutierrez-Hartmann

From the Department of Medicine and Department of Biochemistry, Biophysics and Genetics, Program in Molecular Biology and Colorado Cancer Center, University of Colorado Health Sciences Center, Denver, Colorado 80262

Pit-1, a pituitary-specific POU homeodomain transcription factor, specifies three anterior pituitary lineages; governs growth hormone, prolactin, and thyrotropin gene expression; and mediates basal and Ras-stimulated prolactin promoter activity in GH4 pituitary cells. Alternate splicing of the Pit-1 message produces the Pit-1beta isoform, which contains a 26-amino acid insertion, the beta -domain, within the amino-terminal transactivation domain. The beta -domain functions as a molecular switch, such that Pit-1beta blocks both basal and Ras-stimulated prolactin promoter activity in GH4 pituitary cells yet preferentially enhances protein kinase A-stimulated prolactin promoter activity in a HeLa reconstitution system. To determine whether the amino acid sequence of the beta -domain dictates function, we replaced it with five different 26-amino acid sequences. These mutants fail to block basal or Ras-stimulated rat prolactin promoter activity and fail to optimally enhance the protein kinase A response of prolactin promoter. These data demonstrate that the amino acid sequence of the beta -domain specifies its role as a molecular switch. Additionally, the presence of both Pit-1 and Pit-1beta in pituitary cells allows diverse incoming signals to utilize structurally different forms of the same gene product, which can interact with distinct co-factors, integrating multiple signaling pathways at the level of the nucleus.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 Mol. Endocrinol.Home page
D. L. Duval, M. D. Jonsen, S. E. Diamond, P. Murapa, A. Jean, and A. Gutierrez-Hartmann
Differential Utilization of Transcription Activation Subdomains by Distinct Coactivators Regulates Pit-1 Basal and Ras Responsiveness
Mol. Endocrinol., January 1, 2007; 21(1): 172 - 185.
[Abstract] [Full Text] [PDF]

Home page
 J Mol EndocrinolHome page
R A Sporici, J S Hodskins, D M Locasto, L B Meszaros, A L Ferry, A M Weidner, C A Rinehart, J C Bailey, I M Mains, and S E Diamond
Repression of the prolactin promoter: a functional consequence of the heterodimerization between Pit-1 and Pit-1 {beta}
J. Mol. Endocrinol., October 1, 2005; 35(2): 317 - 331.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
A L Ferry, D M Locasto, L B Meszaros, J C Bailey, M D Jonsen, K Brodsky, C J Hoon, A Gutierrez-Hartmann, and S E Diamond
Pit-1{beta} reduces transcription and CREB-binding protein recruitment in a DNA context-dependent manner
J. Endocrinol., April 1, 2005; 185(1): 173 - 185.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. L. Duval, A. Jean, and A. Gutierrez-Hartmann
Ras Signaling and Transcriptional Synergy at a Flexible Ets-1/Pit-1 Composite DNA Element Is Defined by the Assembly of Selective Activation Domains
J. Biol. Chem., October 10, 2003; 278(41): 39684 - 39696.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
B. Andersen and M. G. Rosenfeld
POU Domain Factors in the Neuroendocrine System: Lessons from Developmental Biology Provide Insights into Human Disease
Endocr. Rev., February 1, 2001; 22(1): 2 - 35.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
A. P. Bradford, K. S. Brodsky, S. E. Diamond, L. C. Kuhn, Y. Liu, and A. Gutierrez-Hartmann
The Pit-1 Homeodomain and beta -Domain Interact with Ets-1 and Modulate Synergistic Activation of the Rat Prolactin Promoter
J. Biol. Chem., February 4, 2000; 275(5): 3100 - 3106.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
S. E. Diamond, M. Chiono, and A. Gutierrez-Hartmann
Reconstitution of the Protein Kinase A Response of the Rat Prolactin Promoter: Differential Effects of Distinct Pit-1 Isoforms and Functional Interaction with Oct-1
Mol. Endocrinol., February 1, 1999; 13(2): 228 - 238.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
R. E. Schweppe, A. A. Frazer-Abel, A. Gutierrez-Hartmann, and A. P. Bradford
Functional Components of Fibroblast Growth Factor (FGF) Signal Transduction in Pituitary Cells. IDENTIFICATION OF FGF RESPONSE ELEMENTS IN THE PROLACTIN GENE
J. Biol. Chem., December 5, 1997; 272(49): 30852 - 30859.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. E. Diamond and A. Gutierrez-Hartmann
The Pit-1beta Domain Dictates Active Repression and Alteration of Histone Acetylation of the Proximal Prolactin Promoter
J. Biol. Chem., September 29, 2000; 275(40): 30977 - 30986.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 1996 by the American Society for Biochemistry and Molecular Biology.