Pathway effects
| Ligands | |
| Receptors |
| Details | Receptor | Ligand | Pathway | Relevance | Pathway effect outcomes | Experiment | Reference | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Details | Class |
Rec Fam | UniProt | IUPHAR | Species | Name | Investigated signalling protein |
Therapeutic area (from Open Targets) |
High level term | Summary | Detailed description | Pathway distinction | System | Assesment method | Authors | DOI |
| 758 Details | Class A (Rhodopsin) | Adrenoceptors | P34971 | ADRB1 | Mouse | carvedilol | β-arrestin | Heart disease | Cardioprotection | β-arr mediated β1AR transactivation of EGFR with following ERK activation leads to cardioprotective effects | Ligand (β-blocker) induce EGFR internalazation | Biased ligand (towards sig. prot.) | Cells | Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) | Kim IM, Tilley DG, Chen J, Salazar NC, Whalen EJ, Violin JD, Rockman HA | 105:14555-60 |
| 758 Details | Class A (Rhodopsin) | Adrenoceptors | P34971 | ADRB1 | Mouse | carvedilol | β-arrestin | Heart disease | Cardioprotection | β-arr mediated β1AR transactivation of EGFR with following ERK activation leads to cardioprotective effects | Ligand (β-blocker) induce EGFR transactivation and ERK activation | Biased ligand (towards sig. prot.) | Cells | Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) | Kim IM, Tilley DG, Chen J, Salazar NC, Whalen EJ, Violin JD, Rockman HA | 105:14555-60 |
| 758 Details | Class A (Rhodopsin) | Adrenoceptors | P34971 | ADRB1 | Mouse | carvedilol | β-arrestin | Heart disease | Cardioprotection | β-arr mediated β1AR transactivation of EGFR with following ERK activation leads to cardioprotective effects | Ligand (β-blocker) significantly increased ERK activation in mouse heart | Biased ligand (towards sig. prot.) | Animals | Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) | Kim IM, Tilley DG, Chen J, Salazar NC, Whalen EJ, Violin JD, Rockman HA | 105:14555-60 |
| 758 Details | Class A (Rhodopsin) | Adrenoceptors | P34971 | ADRB1 | Mouse | carvedilol | β-arrestin | Heart disease | Cardioprotection | β-arr mediated β1AR transactivation of EGFR with following ERK activation leads to cardioprotective effects | β1ARs without C-tail phosphorylation sites prevent EGFR transactivation | Knock in - mutant receptor with impared signalling | Cells | Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) | Kim IM, Tilley DG, Chen J, Salazar NC, Whalen EJ, Violin JD, Rockman HA | 105:14555-60 |
| 758 Details | Class A (Rhodopsin) | Adrenoceptors | P34971 | ADRB1 | Mouse | carvedilol | β-arrestin | Heart disease | Cardioprotection | β-arr mediated β1AR transactivation of EGFR with following ERK activation leads to cardioprotective effects | siRNS targeting β-arr1, β-arr2 or both significantly blocked ERK activation | Gene silencing (siRNA) of sig. prot. | Cells | Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) | Kim IM, Tilley DG, Chen J, Salazar NC, Whalen EJ, Violin JD, Rockman HA | 105:14555-60 |
| 354 Details | Class A (Rhodopsin) | Adrenoceptors | P34971 | ADRB1 | Mouse | alprenolol | β-arrestin | Heart disease | Cardioprotection | β-arr mediated β1AR transactivation of EGFR with following ERK activation leads to cardioprotective effects | Ligand (β-blocker) induce EGFR internalazation | Biased ligand (towards sig. prot.) | Cells | Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) | Kim IM, Tilley DG, Chen J, Salazar NC, Whalen EJ, Violin JD, Rockman HA | 105:14555-60 |
| 354 Details | Class A (Rhodopsin) | Adrenoceptors | P34971 | ADRB1 | Mouse | alprenolol | β-arrestin | Heart disease | Cardioprotection | β-arr mediated β1AR transactivation of EGFR with following ERK activation leads to cardioprotective effects | Ligand (β-blocker) induce EGFR transactivation and ERK1/2 activation | Biased ligand (towards sig. prot.) | Cells | Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) | Kim IM, Tilley DG, Chen J, Salazar NC, Whalen EJ, Violin JD, Rockman HA | 105:14555-60 |
| 354 Details | Class A (Rhodopsin) | Adrenoceptors | P34971 | ADRB1 | Mouse | alprenolol | β-arrestin | Heart disease | Cardioprotection | β-arr mediated β1AR transactivation of EGFR with following ERK activation leads to cardioprotective effects | Ligand (β-blocker) significantly increased ERK activation in mouse heart | Biased ligand (towards sig. prot.) | Animals | Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) | Kim IM, Tilley DG, Chen J, Salazar NC, Whalen EJ, Violin JD, Rockman HA | 105:14555-60 |
| 354 Details | Class A (Rhodopsin) | Adrenoceptors | P34971 | ADRB1 | Mouse | alprenolol | β-arrestin | Heart disease | Cardioprotection | β-arr mediated β1AR transactivation of EGFR with following ERK activation leads to cardioprotective effects | β1ARs without C-tail phosphorylation sites prevent EGFR transactivation | Knock in - mutant receptor with impared signalling | Cells | Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) | Kim IM, Tilley DG, Chen J, Salazar NC, Whalen EJ, Violin JD, Rockman HA | 105:14555-60 |
| 354 Details | Class A (Rhodopsin) | Adrenoceptors | P34971 | ADRB1 | Mouse | alprenolol | β-arrestin | Heart disease | Cardioprotection | β-arr mediated β1AR transactivation of EGFR with following ERK activation leads to cardioprotective effects | siRNS targeting β-arr1, β-arr2 or both significantly blocked ERK activation | Gene silencing (siRNA) of sig. prot. | Cells | Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) | Kim IM, Tilley DG, Chen J, Salazar NC, Whalen EJ, Violin JD, Rockman HA | 105:14555-60 |
| 1360 Details | Class A (Rhodopsin) | Adrenoceptors | P34971 | ADRB1 | Mouse | dobutamine | β-arrestin | Heart disease | Cardioprotection | β-arrestin–mediated transactivation of the EGFR confers cardioprotection under conditions of catecholamine excess. | β1ARs without C-tail phosphorylation sites prevent EGFR transactivation and internalization plus leads to only minimal ERK activation | Knock in - mutant receptor with impared signalling | Cells | Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) | Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA | 117:2445-58 |
| 1360 Details | Class A (Rhodopsin) | Adrenoceptors | P34971 | ADRB1 | Mouse | dobutamine | β-arrestin | Heart disease | Cardioprotection | β-arrestin–mediated transactivation of the EGFR confers cardioprotection under conditions of catecholamine excess. | Robust membrane translocation of GFP-β-arr | Tagged sig. prot | Cells | Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) | Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA | 117:2445-58 |
| 1360 Details | Class A (Rhodopsin) | Adrenoceptors | P34971 | ADRB1 | Mouse | dobutamine | β-arrestin | Heart disease | Cardioprotection | β-arrestin–mediated transactivation of the EGFR confers cardioprotection under conditions of catecholamine excess. | siRNS targeting β-arr1, β-arr2 or both significantly blocked EGFR transactivation and associated ERK activation | Gene silencing (siRNA) of sig. prot. | Cells | Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) | Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA | 117:2445-58 |
| 1360 Details | Class A (Rhodopsin) | Adrenoceptors | P34971 | ADRB1 | Mouse | dobutamine | β-arrestin | Heart disease | Cardioprotection | β-arrestin–mediated transactivation of the EGFR confers cardioprotection under conditions of catecholamine excess. | siRNA targeting of β-arrestin1/2 blocked EGFR internalization | Gene silencing (siRNA) of sig. prot. | Cells | Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) | Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA | 117:2445-58 |
| 1964 Details | Class A (Rhodopsin) | Adrenoceptors | P34971 | ADRB1 | Mouse | isoprenaline | β-arrestin | Heart disease | Cardioprotection | β-arrestin–mediated transactivation of the EGFR confers cardioprotection under conditions of catecholamine excess. | siRNA targeting of β-arrestin1/2 blocked EGFR internalization | Gene silencing (siRNA) of sig. prot. | Cells | Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) | Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA | 117:2445-58 |
| 1360 Details | Class A (Rhodopsin) | Adrenoceptors | P34971 | ADRB1 | Mouse | dobutamine | β-arrestin-2 | Heart disease | Cardioprotection | β-arrestin–mediated transactivation of the EGFR confers cardioprotection under conditions of catecholamine excess. | ERK activation was completely blocked in the β-arrestin2–knockout mice | Knock out of sig. prot. | Animals | Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) | Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA | 117:2445-58 |
| 1964 Details | Class A (Rhodopsin) | Adrenoceptors | P34971 | ADRB1 | Mouse | isoprenaline | β-arrestin | Heart disease | Cardioprotection | β-arrestin–mediated transactivation of the EGFR confers cardioprotection under conditions of catecholamine excess. | Cardiac contractility was significantly enhanced indicating a state of diminished βAR desensitization | Knock in - mutant receptor with impared signalling | Animals | Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) | Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA | 117:2445-58 |
| 1964 Details | Class A (Rhodopsin) | Adrenoceptors | P34971 | ADRB1 | Mouse | isoprenaline | β-arrestin | Heart disease | Cardioprotection | β-arrestin–mediated transactivation of the EGFR confers cardioprotection under conditions of catecholamine excess. | βAR density reduced in WT after chronic agonist treatment but not in mutant. | Knock in - mutant receptor with impared signalling | Animals | Cell/tissue-based assay (ERK, Ca2+, DNA fragmentation, etc.) | Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA | 117:2445-58 |
| 1964 Details | Class A (Rhodopsin) | Adrenoceptors | P34971 | ADRB1 | Mouse | isoprenaline | β-arrestin | Heart disease | Cardioprotection | β-arrestin–mediated transactivation of the EGFR confers cardioprotection under conditions of catecholamine excess. | Significant deterioration in cardiac function with marked LV dilatation and reduced fractional shortening | Knock in - mutant receptor with impared signalling | Animals | Measurements on living organism (BP, pulse, resp. rate, ECG, etc.) | Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA | 117:2445-58 |
| 1964 Details | Class A (Rhodopsin) | Adrenoceptors | P34971 | ADRB1 | Mouse | isoprenaline | β-arrestin | Heart disease | Cardioprotection | β-arrestin–mediated transactivation of the EGFR confers cardioprotection under conditions of catecholamine excess. | Increased interstitial fibrosis and apoptotic nuclei | Knock in - mutant receptor with impared signalling | Animals | Histological examination | Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA | 117:2445-58 |