ß-Arrestin 2 Regulates Zebrafish Development Through the Hedgehog Signaling Pathway

Abstract

beta-arrestins are multifunctional proteins that act as scaffolds and transducers of intracellular signals from heptahelical transmembrane-spanning receptors (7TMR). Hedgehog (Hh) signaling, which uses the putative 7TMR, Smoothened, is established as a fundamental pathway in development, and unregulated Hh signaling is associated with certain malignancies. Here, we show that the functional knockdown of beta-arrestin 2 in zebrafish embryos recapitulates the many phenotypes of Hh pathway mutants. Expression of wild-type beta-arrestin 2, or constitutive activation of the Hh pathway downstream of Smoothened, rescues the phenotypes caused by beta-arrestin 2 deficiency. These results suggest that a functional interaction between beta-arrestin 2 and Smoothened may be critical to regulate Hh signaling in zebrafish development.

Expression of β-arrestin 1 in Gastric Cardiac Adenocarcinoma and its Relation with Progression

“…β-arrestin 1 acts as a nuclear scaffold that recruits histone acetyl-transferase p300 to the transcription factor CREB, which leads to increased gene expression through the acetylation of histone H4 and chromatin reorganization (Wilbanks et al, 2004). Then, β-arrestin 1 potentially regulates Bcl-2 expression, which is critically involved in regulating the apoptosis of both normal and transformed cells (Shi et al, 2007).…”

“…β-arrestins translocate from the cytoplasm to the nucleus and associate with transcription cofactors such as p300 and cAMP-response element-binding protein (CREB) at the promoters of target genes to promote transcription (Kang et al, 2005). β-arrestins are also involved in the development (Chen et al, 2004;Wilbanks et al, 2004) and cellular movement (Ge et al, 2004;Hunton et al, 2005; This study aims to analyze the expression of β-arrestin 1 in gastric cardiac adenocarcinoma and its relationships with clinicopathologic characteristics and survival status, which might help to investigate the functions of β-arrestin 1 in the differentiation and metastasis progression of gastric cardiac adenocarcinoma.…”

Fetal alcohol exposure impairs hedgehog cholesterol modification and signaling

“…51 Immunohistochemistry is carried out with following primary antibodies (Hybridoma Bank, 1:10): MF20 to stain myocardium and facial muscles, S46 to identify ventricular myocardium, and F59 to identify slow muscle progenitors in the somites. The secondary antibodies were Alexa 568-conjugated goat anti-mouse IgG 2b and Alexa 488-conjugated goat anti-mouse IgG 2a (1:400, Molecular Probes).…”

“…RT-PCR were performed using with primers (Supplementary Table 1) as described previously. 52 Immunoblot Total cellular protein was isolated as described previously 51 and cell membrane proteins were isolated using the Mem-PER(r) Eukaryotic Membrane Protein Extraction Reagent Kit (Pierce Biotechnology). Proteins (40 mg) in Laemmli buffer were then separated by 12% Tris-HCI SDS-polyacrylamide gel electrophoresis and transferred to a PVDF membrane.…”

The Orphan G Protein-coupled Receptor Gpr175 (Tpra40) Enhances Hedgehog Signaling by Modulating cAMP Levels

“…Furthermore, G protein-coupled receptor kinases (GRKs) and ␤-arrestin 2, two classical GPCR-interacting proteins, were shown to interact with Smo to facilitate Hh signaling (28,29). Recently, it was shown that constitutive activation of the GPCR Gpr161 increases cellular cAMP levels via G␣ s , thus increasing activation of PKA and enforcing repression of Hh signaling (30).…”