Regulation of Growth Hormone Signaling by Selective Estrogen Receptor Modulators Occurs through Suppression of Protein Tyrosine Phosphatases

Leung, Kin-Chuen, Brce, Jesena, Doyle, Nathan, Lee, Heather J., Leong, Gary M., Sjögren, Klara and Ho, Ken K. Y. (2007) Regulation of Growth Hormone Signaling by Selective Estrogen Receptor Modulators Occurs through Suppression of Protein Tyrosine Phosphatases. Endocrinology, 148 5: 2417-2423. doi:10.1210/en.2006-1305


Author Leung, Kin-Chuen
Brce, Jesena
Doyle, Nathan
Lee, Heather J.
Leong, Gary M.
Sjögren, Klara
Ho, Ken K. Y.
Title Regulation of Growth Hormone Signaling by Selective Estrogen Receptor Modulators Occurs through Suppression of Protein Tyrosine Phosphatases
Journal name Endocrinology   Check publisher's open access policy
ISSN 0013-7227
1945-7170
Publication date 2007-05
Year available 2007
Sub-type Article (original research)
DOI 10.1210/en.2006-1305
Volume 148
Issue 5
Start page 2417
End page 2423
Total pages 7
Place of publication Chevy Chase, MD, United States
Publisher Endocrine Society
Language eng
Subject 1101 Medical Biochemistry and Metabolomics
Formatted abstract
Activation of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5) pathway by GH is terminated by the suppressors of cytokine signaling (SOCSs) and protein tyrosine phosphatases, Src homology 2 domain-containing protein tyrosine phosphatase (SHP)-1 and SHP-2. Based on our recent report that estrogen inhibits GH signaling by stimulating SOCS-2 expression, we investigated the effects of selective estrogen receptor modulators (SERMs) on GH signaling in human embryonic kidney (HEK293) and breast cancer (MDA-MB-231) cells expressing human GH receptor and estrogen receptor-{alpha}. 17ß-Estradiol (E2) suppressed GH activation of a STAT5-responsive luciferase reporter and JAK2 phosphorylation in both cell models. 4-Hydroxytamoxifen and raloxifene augmented these actions of GH in HEK293 cells but not breast cancer cells. SOCS-2 expression in both cell types was stimulated by E2 but unaffected by SERMs. In HEK293 cells, SHP-1 was inhibited by raloxifene and 4-hydroxytamoxifen, whereas the latter additionally inhibited SHP-2. The phosphatases were unaffected by E2. In breast cancer cells, phosphatase activity was not altered by SERMs or E2. In summary, estrogen inhibited the JAK2/STAT5 signaling of GH and stimulated SOCS-2 expression in both HEK293 and breast cancer cells. By contrast, SERMs augmented GH signaling by reducing SHP activities in HEK293 cells and had no effect on both in breast cancer cells. We provide the first evidence for a novel mechanism regulating GH signaling, in which SERMs enhance GH activation of the JAK2/STAT5 pathway in a cell-type-dependent manner by attenuating protein tyrosine phosphatase activities.
Q-Index Code C1
Institutional Status UQ
Additional Notes Epublished 1 February 2007

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
 
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Created: Mon, 30 Mar 2009, 16:27:03 EST by Mary-Anne Marrington on behalf of Paediatrics & Child Health - Mater Hospital