Projects per year
Abstract
Calcitonin receptor-like receptor (CLR) and the receptor activity-modifying protein 2 (RAMP2) comprise a receptor for adrenomedullin (AM). Although it is known that AM induces internalization of CLR•RAMP2, little is known about the molecular mechanisms that regulate the trafficking of CLR•RAMP2. Using HEK and HMEC-1 cells, we observed that AM-induced activation of CLR•RAMP2 promoted ubiquitination of CLR. A mutant (CLRΔ9KR), lacking all intracellular lysine residues was functional and trafficked similar to the wild-type receptor, but was not ubiquitinated. Degradation of CLR•RAMP2 and CLRΔ9KR•RAMP2 was not dependent on the duration of AM stimulation or ubiquitination and occurred via a mechanism that was partially prevented by peptidase inhibitors. Degradation of CLR•RAMP2 was sensitive to overexpression of hepatocyte growth factor-regulated tyrosine kinase substrate (HRS), but not to HRS knockdown, whereas CLRΔ9KR•RAMP2 degradation was unaffected. Overexpression, but not knockdown of HRS, promoted hyperubiquitination of CLR under basal conditions. Thus, we propose a role for ubiquitin and HRS in the regulation of AM-induced degradation of CLR•RAMP2.
Original language | English |
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Article number | 12389 |
Pages (from-to) | 1-18 |
Number of pages | 18 |
Journal | Open Access Scientific Reports |
Volume | 7 |
Issue number | 1 |
DOIs | |
Publication status | Published - 28 Sept 2017 |
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Dive into the research topics of 'The Role of Ubiquitination and Hepatocyte Growth Factor-Regulated Tyrosine Kinase Substrate in the Degradation of the Adrenomedullin Type I Receptor'. Together they form a unique fingerprint.Projects
- 1 Finished
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Investigation of the Mechanisms and Functions of the Post-Endocytic Sorting of the Receptors - Fellowship for Dr G Cottrell
Cottrell, G. (PI) & Garland, C. J. (CoI)
1/12/08 → 30/11/12
Project: UK charity
Profiles
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Stephen Ward
- Department of Life Sciences - Professor
- Centre for Therapeutic Innovation
- Centre for Bioengineering & Biomedical Technologies (CBio)
Person: Research & Teaching, Affiliate staff
Equipment
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Confocal Laser Scanning Confocal Microscope (LSM)
Material and Chemical Characterisation (MC2)Facility/equipment: Equipment
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MC2-Bioimaging and cell analysis
Material and Chemical Characterisation (MC2)Facility/equipment: Technology type