Korean Circ J.  2018 Apr;48(4):325-328. 10.4070/kcj.2018.0057.

You're Not under Arrest: Worry-free with β-arrestin

• Marquez J
• Han J

• KMID: 2407902
• DOI: http://doi.org/10.4070/kcj.2018.0057

Abstract

No abstract available.

Figure

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  Figure 1 β-arr is a potential therapeutic target for various diseases. (A) β-arr signaling in cancer cells. When a peptide such a obestatin binds to a receptor, phosphorylation of GPCR occurs leading to the attraction of β-arr. β-arr is then translocated which allows for its association with Src. The β-arr/Src interaction results in EGFR transactivation and Akt signaling. (B) β-arr signaling in mature cardiac cells. Catecholamines (e.g., epinephrine) can elicit a reaction through G-protein signaling or through β-arr2-mediated signaling which leads to improved cardiac response and contractility. Wound-healing associated inflammation also occurs via NF-κB pathway as activated by β-arr2, which are essential to preservation of cardiac function post-MI. (C) β-arr signaling in cancer stem cells. When CXCL12 binds to CXCR7, β-arr pathway is activated through GRK to internalize CXCR7 resulting in CXCL12 scavenging. It can also signal PLC to activate ERK 1/2 which leads to cell survival in certain cancer cells (for example, glioblastoma). (D) β-arr signaling in metoprolol-mediated cardiac fibrosis. Cardiac fibrosis induced by metoprolol via GRK5/β-arr2 is fairly miniscule compared to the fibrosis caused by heart failure. In addition, β-blocking capacity by metoprolol induces a positive action that can overshadow the fibrosis induced. (E) Possible β-arr signaling in cardiac progenitor cells. β-arr2 can affect expression of β-catenin via PI3K/GSK-3β signaling, resulting in cell survival brought about by regulation of cell mobility and tube formation. An alternative pathway can trigger β-arr-dependent ERK signaling via ERK 1/2. AC = adenylyl cyclase; Akt = protein kinase B; ATP = adenosine triphosphate; cAMP = cyclic adenosine monophosphate; COL1 = collagen 1; c-Src = proto-oncogene tyrosine-protein kinase Src; CXCL12 = C-X-C motif chemokine ligand 12; CXCR4 = C-X-C chemokine receptor type 4; CXCR7 = C-X-C chemokine receptor type 7; EGFR = epithelial growth factor receptor; ERK = extracellular signal-regulated kinase; GPCR = G-protein-coupled receptor; GRK = G protein-coupled receptor kinase; GSK-3β = glycogen synthase kinase-3β; Iκβα = nuclear factor κB inhibitor of nuclear factor κB; MEK = mitogen-activated protein kinase kinase; MI = myocardial infarction; mLST8 = mammalian lethal with SEC13 protein-8; mTOR = mechanistic target of rapamycin; NF-κB = nuclear factor-κB; p70s6k = 70 kDa ribosomal S6 kinase; PI3K = phosphoinositide 3-kinase; PKA = protein kinase A; PLC = phospholipase C; RAF = rapidly accelerated fibrosarcoma; Raptor = regulatory associated protein of mTOR; TGF = transforming growth factor; βAR = β-adrenergic receptor; β-arr = β-arrestin; β-catenin = β-catenin.

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