Please use this identifier to cite or link to this item:
|Title:||Nuclear translocation and retention of growth hormone||Authors:||Mertani, H.C.
|Issue Date:||1-Jul-2003||Citation:||Mertani, H.C., Raccurt, M., Abbate, A., Kindblom, J., Törnell, J., Billestrup, N., Usson, Y., Morel, G., Lobie, P.E. (2003-07-01). Nuclear translocation and retention of growth hormone. Endocrinology 144 (7) : 3182-3195. ScholarBank@NUS Repository. https://doi.org/10.1210/en.2002-221121||Abstract:||We have previously demonstrated that GH is subject to rapid receptor-dependent nuclear translocation. Here, we examine the importance of ligand activation of the GH-receptor (GHR)-associated Janus kinase (JAK) 2 and receptor dimerization for hormone internalization and nuclear translocation by use of cells stably transfected with cDNA for the GHR. Staurosporine and herbimycin A treatment of cells did not affect the ability of GH to internalize but resulted in increased nuclear accumulation of hormone. Similarly, receptor mutations, which prevent the association and activation of JAK2, did not affect the ability of the hormone to internalize or translocate to the nucleus but resulted in increased nuclear accumulation of GH. These results were observed both by nuclear isolation and confocal laser scanning microscopy. Staurosporine treatment of cells in which human GH (hGH) was targeted to the cytoplasm (removal of secretion sequence) or to the nucleus (addition of the nuclear localization sequence of SV40 large T antigen) resulted in preferential accumulation of hGH in the nucleus. We further investigated the requirement of receptor dimerization for GH nuclear translocation using the non-receptor-dimerizing hGH antagonist, hGH-G120R, conjugated to fluorescein isothiocyanate. Confocal laser scanning microscopy demonstrated efficient internalization of both hGH and hGH-G120R but lack of nuclear translocation of hGH-G120R. Thus, we conclude that activation of JAK2 kinase and the subsequent tyrosine phosphorylation is not required for nuclear translocation of GH but is pivotal for the removal of the hormone from the nucleus, and that GH translocates into the nucleus in a GHR dimerized-dependent fashion.||Source Title:||Endocrinology||URI:||http://scholarbank.nus.edu.sg/handle/10635/113569||ISSN:||00137227||DOI:||10.1210/en.2002-221121|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Jul 29, 2021
WEB OF SCIENCETM
checked on Jul 29, 2021
checked on Aug 1, 2021
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.