| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 278, Issue 8, 6346-6354, February 21, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the In the rat, a growth hormone-binding protein
(GHBP) exists that is derived from the growth hormone (GH) receptor
gene by an alternative mRNA splicing mechanism such that the
transmembrane and intracellular domains of the GH receptor are replaced
by a hydrophilic carboxyl terminus. In isolation, the GHBP is inactive, although it does compete with the receptor for ligand binding in the
extracellular space and therefore inhibits the cellular response to GH.
The GHBP is also located intracellularly and is translocated to the
nucleus upon ligand stimulation. We show here that endogenously
produced GHBP, in contrast to exogenous GHBP, was able to enhance the
STAT5-mediated transcriptional response to GH. Interestingly, when the
GHBP was targeted constitutively to the nucleus by the addition of the
nuclear localization sequence of the SV40 large T antigen,
greater enhancement of STAT5-mediated transcription was obtained. The
transcriptional enhancement did not require GH per se and
was not specific to the GH receptor, since similar enhancement of
STAT5-mediated transcription by nuclear localized GHBP was obtained
with specific ligand stimulation of both prolactin and erythropoietin
receptors. Thus, the GHBP exerts divergent effects on STAT5-mediated
transcription depending on its cellular location. The use of a soluble
cytokine receptor as a location-dependent transcriptional
enhancer and the ligand-independent involvement of the extracellular
domain of a polypeptide ligand receptor in intracellular signal
transduction provide additional novel mechanisms of transcriptional control.
The Growth Hormone-binding Protein Is a
Location-dependent Cytokine Receptor Transcriptional
Enhancer*
,,
Institute of Molecular and Cell Biology,
117609 Singapore, Republic of Singapore and the Departments of
§ Physiology and ¶ Internal Medicine, Sahlgrenska
University Hospital, University of Göteborg,
Göteborg S-41345, Sweden
*
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Institute of
Molecular and Cell Biology, National University of Singapore, 30 Medical Dr., Singapore 117609, Republic of Singapore. Tel.:
65-68747847; Fax: 65-67791117; E-mail: mcbpel@imcb.nus.edu.sg.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  B. L. Conway-Campbell, A. J. Brooks, P. J. Robinson, M. Perani, and M. J. Waters The Extracellular Domain of the Growth Hormone Receptor Interacts with Coactivator Activator to Promote Cell Proliferation Mol. Endocrinol., September 1, 2008; 22(9): 2190 - 2202. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kawai, N. Namba, S. Mushiake, Y. Etani, R. Nishimura, M. Makishima, and K. Ozono Growth hormone stimulates adipogenesis of 3T3-L1 cells through activation of the Stat5A/5B-PPAR{gamma} pathway J. Mol. Endocrinol., January 1, 2007; 38(1): 19 - 34. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-C. Leung, G. Johannsson, G. M. Leong, and K. K. Y. Ho Estrogen Regulation of Growth Hormone Action Endocr. Rev., October 1, 2004; 25(5): 693 - 721. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. C. Mertani, M. Raccurt, A. Abbate, J. Kindblom, J. Tornell, N. Billestrup, Y. Usson, G. Morel, and P. E. Lobie Nuclear Translocation and Retention of Growth Hormone Endocrinology, July 1, 2003; 144(7): 3182 - 3195. [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 |
