Novel alpha1-adrenergic receptor signaling pathways: secreted factors and interactions with the extracellular matrix

Molecular Pharmacology
Ting ShiDianne M Perez

Abstract

alpha1-Adrenergic receptor (alpha1-ARs) subtypes (alpha1A, alpha1B, and alpha1D) regulate multiple signal pathways, such as phospholipase C, protein kinase C (PKC), and mitogen-activated protein kinases. We employed oligonucleotide microarray technology to explore the effects of both short- (1 h) and long-term (18 h) activation of the alpha1A-AR to enable RNA changes to occur downstream of earlier well characterized signaling pathways, promoting novel couplings. Polymerase chain reaction (PCR) studies confirmed that PKC was a critical regulator of alpha1A-AR-mediated gene expression, and secreted interleukin (IL)-6 also contributed to gene expression alterations. We next focused on two novel signaling pathways that might be mediated through alpha1A-AR stimulation because of the clustering of gene expression changes for cell adhesion/motility (syndecan-4 and tenascin-C) and hyaluronan (HA) signaling. We confirmed that alpha1-ARs induced adhesion in three cell types to vitronectin, an interaction that was also integrin-, FGF7-, and PKC-dependent. alpha1-AR activation also inhibited cell migration, which was integrin- and PKC-independent but still required secretion of FGF7. alpha1-AR activation also increased the expression and d...Continue Reading

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Citations

Apr 18, 2014·PloS One·Yunlong MaXiangdong Ding
Mar 31, 2016·Biophysical Journal·Hengameh ShamsMohammad R K Mofrad
Jul 2, 2014·Drug Discovery Today·Mark MinieRam Samudrala
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Jul 29, 2008·Connective Tissue Research·Tiina A JokelaMarkku I Tammi
Nov 17, 2009·The Journal of Allergy and Clinical Immunology·Rasika A MathiasKathleen C Barnes

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