Four distinct mammalian arrestin proteins are known. Arrestin 1 (also known as S-arrestin) and arrestin 4 (or X-arrestin) are localized to retinal rods and cones, respectively. Arrestin 2 (also known as β-arrestin 1) and arrestin 3 (or β-arrestin 2) are ubiquitously expressed and bind to most GPCRs. Members of arrestin/b-arrestin protein family are thought to participate in agonist-mediated desensitization of G-protein-coupled receptors and cause specific dampening of cellular responses to stimuli such as hormones, neurotransmitters, or sensory signals. β-arrestin 1 is a cytosolic protein and acts as a cofactor in the beta-adrenergic receptor kinase (BARK) mediated desensitization of beta-adrenergic receptors. Besides the central nervous system, it is expressed at high levels in peripheral blood leukocytes, and thus the BARK/b-arrestin system is believed to play a major role in regulating receptor-mediated immune functions.  β-arrestin 2 is expressed at high levels in the central nervous system and may play a role in the regulation of synaptic receptors.  β-arrestin proteins function as adapters and scaffold proteins and play important roles in other processes, such as recruiting c-Src family proteins to GPCRs in ERK activation pathways. β-arrestins are also involved in some receptor tyrosine kinase signaling pathways. Additional evidence suggests that β-arrestin proteins translocate to the nucleus and help regulate transcription by binding transcriptional cofactors. Alternatively spliced transcripts encoding different isoforms of b-arrestin 1/2 have been described.

1. Shenoy SK and Lefkowitz RJ. 2005. Sci STKE 308:cm10.
2. Lefkowitz RJ and Shenoy SK. 2005. Science 308:512.
3. Kang J, et al. 2005. Cell 123:833.
4. Szereszewski JM, et al. 2010. PLoS One 5:e12964.
5. Rajagopal S, et al. 2010. P. Natl. Acad. Sci. USA 107:628.
6. McCormick PJ, et al. 2009. PLoS One 4:e8102.