The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

1Alpha,25-dihydroxyvitamin D3 inhibits GH-induced expression of SOCS-3 and CIS and prolongs growth hormone signaling via the Janus kinase (JAK2)/signal transducers and activators of transcription (STAT5) system in osteoblast-like cells.

Growth hormone (GH) and 1alpha,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) are regulators of bone growth and bone metabolism. In target cells, GH activates several signaling pathways, among them the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway. GH mainly activates JAK2 and STAT5a and b. The effects of 1,25-(OH)(2)D(3) are mediated via a nuclear receptor, the vitamin D receptor, which, when bound by 1,25-(OH)(2)D(3), activates the transcription of target genes. In earlier studies (Morel, G., Chavassieux, P., Barenton, B., Dubois, P. M., Meunier, P. J., and Boivin, G. (1993) Cell Tissue Res. 273, 279-286) synergistic interaction between 1,25-(OH)(2)D(3) and GH regarding expression of osteoblastic markers has been described. The UMR 106 cell line is a rat osteosarcoma cell line with osteoblast-like properties. We have recently shown (Morales, O., Lindgren, U., and Haldosen, L. A. (2000) J. Bone Miner. Res. 15, 2284-2290) that UMR 106 cells express a GH-responsive JAK2/STAT5 signaling system. These cells also express the vitamin D receptor and respond to 1,25-(OH)(2)D(3). In the present study we have investigated whether 1,25-(OH)(2)D(3) influences GH signaling via the JAK2/STAT5 pathway in UMR 106 cells. We found that 1,25-(OH)(2)D(3) prolonged GH signaling via the JAK2/STAT5 pathway. Pretreatment of cells with 1,25-(OH)(2)D(3) was also necessary in order to detect GH-induced STAT5 transcriptional response. Furthermore, the pretreatment of cells with 1,25-(OH)(2)D(3) rendered to the cells the capacity to respond to repetitive GH-stimulation. In UMR 106 cells, GH induced the expression of the JAK/STAT negative regulatory proteins SOCS-3 and CIS. Interestingly, pretreatment with 1,25-(OH)(2)D(3) inhibited GH-induced expression of these proteins. From these results we propose that 1,25-(OH)(2)D(3) has an inhibitory effect on negative regulatory pathways acting on JAK2 and/or STAT5 in UMR 106 cells and that this, in all or partly, explains the effects of 1,25-(OH)(2)D(3) on GH-signaling via the JAK/STAT pathway.[1]


WikiGenes - Universities