Cannon, Barbara, and Jan Nedergaard. Brown Adipose Tissue: Function and Physiological Significance. Physiol Rev 84: 277–359, 2004; 10.1152/physrev.00015.2003.—The function of brown adipose tissue i...

Brown Adipose Tissue: Function and Physiological Significance

Seven-transmembrane receptors, which constitute the largest, most ubiquitous and most versatile family of membrane receptors, are also the most common target of therapeutic drugs. Recent findings indicate that the classical models of G-protein coupling and activation of second-messenger-generating enzymes do not fully explain their remarkably diverse biological actions.

Seven-transmembrane receptors.

https://www.cell.com/trends/pharmacological-sciences/pdf/S0165-6147(00)01678-3.pdf

G-protein-coupled receptors and signaling networks: emerging paradigms.

β-Arrestins, originally discovered in the context of heterotrimeric guanine nucleotide binding protein–coupled receptor (GPCR) desensitization, also function in internalization and signaling of these receptors. We identified c-Jun amino-terminal kinase 3 (JNK3) as a binding partner of β-arrestin 2 using a yeast two-hybrid screen and by coimmunoprecipitation from mouse brain extracts or cotransfected COS-7 cells. The upstream JNK activators apoptosis signal–regulating kinase 1 (ASK1) and mitogen-activated protein kinase (MAPK) kinase 4 were also found in complex with β-arrestin 2. Cellular transfection of β-arrestin 2 caused cytosolic retention of JNK3 and enhanced JNK3 phosphorylation stimulated by ASK1. Moreover, stimulation of the angiotensin II type 1A receptor activated JNK3 and triggered the colocalization of β-arrestin 2 and active JNK3 to intracellular vesicles. Thus, β-arrestin 2 acts as a scaffold protein, which brings the spatial distribution and activity of this MAPK module under the control of a GPCR.

https://science.sciencemag.org/content/sci/290/5496/1574.full.pdf

β-Arrestin 2: A Receptor-Regulated MAPK Scaffold for the Activation of JNK3

The D1-like (D1, D5) and D2-like (D2, D3, D4) classes of dopamine receptors each has shared signaling properties that contribute to the definition of the receptor class, although some differences among subtypes within a class have been identified. D1-like receptor signaling is mediated chiefly by the heterotrimeric G proteins Gαs and Gαolf, which cause sequential activation of adenylate cyclase, cylic AMP-dependent protein kinase, and the protein phosphatase-1 inhibitor DARPP-32. The increased phosphorylation that results from the combined effects of activating cyclic AMP-dependent protein kinase and inhibiting protein phosphatase 1 regulates the activity of many receptors, enzymes, ion channels, and transcription factors. D1 or a novel D1-like receptor also signals via phospholipase C-dependent and cyclic AMP-independent mobilization of intracellular calcium. D2-like receptor signaling is mediated by the heterotrimeric G proteins Gαi and Gαo. These pertussis toxin-sensitive G proteins regulate some effec...

Dopamine receptor signaling.

The β2-Adrenergic Receptor Mediates Extracellular Signal-regulated Kinase Activation via Assembly of a Multi-receptor Complex with the Epidermal Growth Factor Receptor

A. Musa Zamah

Papers

The β2-Adrenergic Receptor Mediates Extracellular Signal-regulated Kinase Activation via Assembly of a Multi-receptor Complex with the Epidermal Growth Factor Receptor

Protein kinase A-mediated phosphorylation of the β2-adrenergic receptor regulates its coupling to Gs and Gi: Demonstration in a reconstituted system