Activation of the signal transducers and activators of transcription signaling pathway by growth hormone (GH) in skin fibroblasts from normal and GH binding protein-positive Laron Syndrome children

Endocrinology
J S FreethP E Clayton

Abstract

We have previously described two families (H and M) with GH binding protein-positive Laron Syndrome (LS), proposed to have one or more post GHR signaling defects. In the present study, we have examined whether the signal transducers and activators of transcription (STAT) pathway is activated by GH in skin fibroblast cultures established from these LS children, to determine the level(s) at which GH insensitivity has occurred. On immunoblots, both normal and LS fibroblasts express JAK2 and STATs 1, 3, and 5. GH induced rapid tyrosine phosphorylation of a protein at approximately 93 kDa in normal fibroblasts, and Western blotting with STAT-specific antibodies revealed STAT5 activation (phosphorylation) by GH. To determine further the identity and the DNA binding characteristics of the STAT proteins that were activated by GH, EMSAs were performed using three DNA elements known to bind STAT proteins; m67, the high affinity c-sis-inducible element (SIE), the interferon response element (IRE), and the lactogenic hormone-responsive region (LHRR). GH failed to induce protein binding to the SIE or IRE in normal skin fibroblasts but did induce the formation of a specific complex with the LHRR. Induction by GH of this LHRR/protein complex,...Continue Reading

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Citations

Feb 3, 2005·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Ron G RosenfeldVivian Hwa
Feb 5, 2016·Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society·Paula OcaranzaFernando Cassorla
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Apr 15, 2000·Arteriosclerosis, Thrombosis, and Vascular Biology·R BaettaE Cattaneo
Aug 4, 2006·The FEBS Journal·Andrea P Rojas-GilBessie E Spiliotis
Feb 28, 2002·Endocrinology·Váronique BeauloyeJean-Paul Thissen
Jun 20, 2002·Endocrinology·Corinne M SilvaPeter E Clayton
Nov 24, 1999·The Journal of Clinical Endocrinology and Metabolism·K IidaK Chihara
Dec 13, 2003·Endocrine Reviews·Stephanie R EdmondsonChristopher J Wraight
Sep 30, 2008·Arquivos brasileiros de endocrinologia e metabologia·Alexander Augusto de Lima Jorge
Jun 27, 2002·American Journal of Pharmacogenomics : Genomics-related Research in Drug Development and Clinical Practice·Gerhard Baumann

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