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Title: The growth hormone-binding protein is a location-dependent cytokine receptor transcriptional enhancer
Authors: Graichen, R.
Sandstedt, J.
Goh, E.L.K.
Isaksson, O.G.P.
Törnell, J.
Lobie, P.E. 
Issue Date: 21-Feb-2003
Citation: Graichen, R., Sandstedt, J., Goh, E.L.K., Isaksson, O.G.P., Törnell, J., Lobie, P.E. (2003-02-21). The growth hormone-binding protein is a location-dependent cytokine receptor transcriptional enhancer. Journal of Biological Chemistry 278 (8) : 6346-6354. ScholarBank@NUS Repository.
Abstract: 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.
Source Title: Journal of Biological Chemistry
ISSN: 00219258
DOI: 10.1074/jbc.M207546200
Appears in Collections:Staff Publications

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