P-Arrestins

Some forms of internalization are also arrestin-mediated. GRK-mediated phosphorylation of the receptor is reqnired to promote the formation of the P-arrestin complex that can be internalized (151,152). The pathway of arrestin-mediated GPCR internalization that involves the transfer of ligand-activated receptors from the plasma membrane to an intracellnlar compartment (153) is shown in Fig. 6.2. 

Lefkowitz, R.J. (1998) G protein-coupled receptors new roles for receptor kinases and P-arrestins in receptor signaling and desensitization. / Biol Chem 273(30) 18677-18680. 

The primary function of GRK-mediated receptor phosphorylation is to promote the recruitment of another crucial protein, named P-arrestin,to the activated receptor. Arrestin binds to GPCRs and inhibits further coupling to G proteins hence desensitizing the response (Ferguson 2001 Penn et al. 2001 Pierce et al. 2002 Maudsley et al. 2005). P-arrestin belongs to the arrestin family of which four members have been identified (Gurevich et al. 2008). 

Fig. 5.5 Desensitization of the activated (Tadrenergic receptor, PAR. PARK is the p-adrenergic receptor kinase, as and py are the activated a-subunit and the Py-subunits of the heterotrimeric G protein, Gg. AC is the activated effector, the enzyme adenylyl cyclase. Phosphorylation of activated GPCRs enhances binding of a family of proteins, the arrestins, which prevent access of G proteins and uncouple the receptor from G proteins. The arrestin involved in the desensitization of the P-adrenergic receptor is p-arrestin. (Reproduction of this scheme has been made possible through the generosity of Professor Martin Lohse, Department of Pharmacology, University of Wurzburg, Medical School.)...

Lefkowitz RK, Shenoy SK (2005) Transduction of receptor signals by P-arrestins. Science 308 512-517. 

Ahn S, Nelson CD, Garrison TR, Miller WE, Lefkowitz RJ. Desensitization, internalization, and signaling functions of P-arrestins demonstrated by RNA interference. Proc Natl Acad Sci U S A 2003 100 1740-1744. 

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