Examples of receptor phosphorylation at C-terminus and corresponding functions
| GPCR | Phosphorylation Sites | Kinase | Method | Cell Type | Function | References |
|---|---|---|---|---|---|---|
| Angiotensin II receptor type I (AT1aR) | T332, S335, T336, S338 | PKC/GRK | Mut | CHO | Internalization | (Thomas et al., 1998) |
| S331, S338, S348 | PKC | Mut | CHO | ND | (Qian et al., 1999) | |
| β2 adrenergic receptor (β2AR) | S345, S346 | PKA | Mut | Mouse L cells | Desensitization | (Clark et al., 1989) |
| S355, S356, S364 | GRK | Mut | HEK293 | Desensitization | (Seibold et al., 2000) | |
| S355, S356 | GRK6 | MS and P-SA | HEK293 | Desensitization and β-arrestin-mediated ERK1/2 activation | (Nobles et al., 2011) | |
| In vitro | β-arrestin-1 mediated SRC activation | (Yang et al., 2015) | ||||
| T360, S364, S396, S401, S407, S411 | GRK2 | MS and P-SA | HEK293 | Desensitization and internalization | (Nobles et al., 2011) | |
| In vitro | β-arrestin-1 mediated clathrin recruitment and internalization | (Yang et al., 2015) | ||||
| T384, S396, S401, and S407 | GRK2 | PAA | In vitro | ND | (Fredericks et al., 1996) | |
| T384, T393, S396, S401, S407, S411 | GRK5 | PAA | In vitro | ND | (Fredericks et al., 1996) | |
| C-X-C motif chemokine receptor type 4 (CXCR-4) | S324, S325 | PKC/GRK6 | MS and P-SA | HEK293 | Receptor degradation | (Busillo et al., 2010) |
| S330/339, cluster S346-S352 | GRK2/6 | MS and P-SA | HEK293 | β-arrestin-2 recruitment and calcium mobilization | (Busillo et al., 2010) | |
| S330/339, cluster S346-S352 | GRK3/6 | MS and P-SA | HEK293 | β-arrestin-1 mediated ERK1/2 activation | (Busillo et al., 2010) | |
| Dopamine receptor D1 (DRD1) | T347 | ND | Mut | HEK293 | Promote secondary phosphorylation of residues within the ICL3 | (Kim et al., 2004) |
| T360 | GRK2 | Mut | CHO | Desensitization | (Lamey et al., 2002) | |
| T428, S431 | GRK4 | Mut | HEK293T | β-arrestin-1 mediated internalization | (Rankin et al., 2006) | |
| S431, T439, T446 | ND | Mut | CHO | Internalization | (Lamey et al., 2002) | |
| Follicle-stimulating hormone receptor (FSHR) | Cluster T638-T644 | GRK2 | Mut | HEK293 | β-arrestin-mediated desensitization and internalization | (Kara et al., 2006) |
| GABAB receptor (GABABR) | S783 | AMPK | MS and EDA | Rat hippocampal neurons | Receptor recycling | (Terunuma et al., 2010) |
| S867 | CaMKII | MS | Rat hippocampal neurons | Internalization | (Guetg et al., 2010) | |
| S892 | PKA | Mut | HEK293 | Internalization | (Couve et al., 2002) | |
| Ghrelin receptor type 1a (GHSR1a) | S349, T350 | ND | MS | HEK293 | Stabilization of the receptor-β-arrestin1/2 complex | (Bouzo-Lorenzo et al., 2016) |
| S362, S363, T366 | ND | MS | HEK293 | β-arrestin1/2 binding and internalization | (Bouzo-Lorenzo et al., 2016) | |
| G protein-coupled receptor 120 (GPR120) | T347, S350, S357 | PKC/GRK6 | Mut | HEK293 | β-arrestin-2 recruitment and calcium mobilization | (Burns et al., 2014) |
| T347, T349, S350 | ND | MS | CHO Flp-In cells | β-arrestin-2 recruitment and Akt activation | (Prihandoko et al., 2016) | |
| S357, S361 | ND | MS | CHO Flp-In cells | β-arrestin-2 recruitment and internalization | (Prihandoko et al., 2016) | |
| μ-opioid receptor (MOR) | S356, S357, S363 | PKC | MS | HEK293 | Desensitization | (Wang et al., 2002; Chen et al., 2013) |
| T370 | CaMKII | MS | HEK293 | ND | (Chen et al., 2013) | |
| S375 | GRK2 | MS | HEK293 | β-arrestin-2 recruitment and desensitization | (Chen et al., 2013; Lowe et al., 2015) | |
| Thyrotropin-releasing hormone receptor (TRHR) | S355, S360, S364, T365 | GRK2 | Mut and P-SA | CHO | β-arrestin-2-mediated desensitization and internalization | (Jones et al., 2007) |
| T365, T371, S383 | CK2 | Mut | COS-1 | β-arrestin-1-dependent internalization | (Hanyaloglu et al., 2001) | |
| Orexin-2 receptor (OX2R) | Cluster T399-S403 | GRK | Mut | HEK293FT | ND | (Jaeger et al., 2014) |
| Cluster S406-T409, Cluster T427-T431 | GRK | Mut | HEK293FT | Receptor-β-arrestin1/2-ubiquitin complex formation | (Jaeger et al., 2014) |
AMPK, 5ʹ-AMP-activated protein kinase; CaMKII, Ca2+/calmodulin-dependent protein kinase II; CHO, Chinese hamster ovary cells; CK2, casein kinase II; COS-1, CV-1 in origin with SV40 genes monkey kidney cells; EDA, Edman degradation analysis; HEK293, human embryonic kidney 293 cells; Mut, mutagenesis; MS, mass spectrometry; ND, not determined; P-SA, phospho-specific antibody; PAA, phospho-amino acid analysis.