Deletion of IGF-I receptor (IGF-IR) in primary osteoblasts reduces GH-induced STAT5 signaling.

Molecular Endocrinology
Yujun GanStuart J Frank

Abstract

GH promotes longitudinal growth and regulates multiple cellular functions in humans and animals. GH signals by binding to GH receptor (GHR) to activate the tyrosine kinase, Janus kinase 2 (JAK2), and downstream pathways including signal transducer and activator of transcription 5 (STAT5), thereby regulating expression of genes including IGF-I. GH exerts effects both directly and via IGF-I, which signals by activating the IGF-I receptor (IGF-IR). IGF-IR is a cell surface receptor that contains intrinsic tyrosine kinase activity within its intracellular domain. In this study, we examined the potential role of IGF-IR in facilitating GH-induced signal transduction, using mouse primary calvarial osteoblasts with Lox-P sites flanking both IGF-IR alleles. These cells respond to both GH and IGF-I and in vitro infection with an adenovirus that drives expression of Cre recombinase (Ad-Cre) dramatically reduces IGF-IR abundance without affecting the abundance of GHR, JAK2, STAT5, or ERK. Notably, infection with Ad-Cre, but not a control adenovirus, markedly inhibited acute GH-induced STAT5 activity (more than doubling the ED(50) and reducing the maximum activity by nearly 50%), while sparing GH-induced ERK activity, and markedly inhibited...Continue Reading

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Citations

Dec 25, 2012·Journal of Neural Transmission·Paige BeckEdgar Garcia-Rill
Nov 16, 2013·Cellular and Molecular Life Sciences : CMLS·H Al-KharobiJ Beattie
Aug 2, 2015·General and Comparative Endocrinology·José Luis Luna-AcostaCarlos Arámburo
Apr 3, 2015·Journal of Cellular Physiology·Ross DobieColin Farquharson
Jan 29, 2014·JAK-STAT·Pramod DarvinYoung Mok Yang
Apr 15, 2016·Molecular Endocrinology·Yue ZhangStuart J Frank
Oct 21, 2015·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Zhongbo LiuShoshana Yakar
Sep 12, 2014·Molecular Endocrinology·Yujun GanStuart J Frank
Sep 1, 2013·Bone Research·Yongmei WangWenhan Chang
Apr 20, 2019·Endocrinology·Vera ChesnokovaShlomo Melmed
Aug 25, 2020·Molecular and Cellular Endocrinology·Stuart J Frank

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