PCSK9 binds LDLR

Stable Identifier
R-HSA-6784734
Type
Reaction [binding]
Species
Homo sapiens
Compartment
ReviewStatus
5/5
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
PCSK9 (Proprotein convertase subtilisin/kexin type 9) binds to LDLR (Low-density lipoprotein receptor) on the cell surface. The binding site of PCSK9 has been localized to the epidermal growth factor-like repeat A (EGF-A) domain of the LDLR (Zhang et al. 2007). The complex PCSK9:LDLR is internalized via clathrin-mediated endocytosis and then routed to lysosomes via a mechanism that does not require ubiquitination and is distinct from the autophagy and proteosomal degradation pathways. In lysosomes, the affinity of the interaction between PCSK9 and LDLR dramatically increases. This promotes the final degradation of PCSK9 and LDLR without recycling. Monoclonal antibodies targeting PCSK9 have been shown to markedly reduce LDL cholesterol levels and are a novel treatment strategy for adults with hypercholesterolemia (Navarese et al. 2015).
Literature References
PubMed ID Title Journal Year
25915661 Effects of Proprotein Convertase Subtilisin/Kexin Type 9 Antibodies in Adults With Hypercholesterolemia: A Systematic Review and Meta-analysis

Kolodziejczak, M, Schulze, V, Brockmeyer, M, Kubica, JM, Gurbel, PA, Lin, Y, Tantry, U, D'Agostino, RB, Kandzari, DE, Navarese, EP, Kubica, J, Volpe, M, Kereiakes, DJ, Agewall, S, Kelm, M

Ann. Intern. Med. 2015
17452316 Binding of proprotein convertase subtilisin/kexin type 9 to epidermal growth factor-like repeat A of low density lipoprotein receptor decreases receptor recycling and increases degradation

Garuti, R, Hobbs, HH, Horton, JD, Zhao, Z, Cohen, JC, Zhang, DW, McDonald, M, Lagace, TA

J. Biol. Chem. 2007
Participants
Participates
Orthologous Events
Authored
Reviewed
Created
Cite Us!