ArticleThe Journal of biological chemistry2014
A hyaluronan receptor for endocytosis (HARE) link domain N-glycan is required for extracellular signal-regulated kinase (ERK) and nuclear factor-κB (NF-κB) signaling in response to the uptake of hyaluronan but not heparin, dermatan sulfate, or acetylated low density lipoprotein (LDL).
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 21 citations in OpenAlex.
- Hyaluronan: An Architect and Integrator for Cancer and Neural Diseases.International journal of molecular sciences · 2025Review
- FTH1 protects against osteoarthritis by MAPK pathway inhibition of extracellular matrix degradation.BMC musculoskeletal disorders · 2024Article
- Chloroquine and cytosolic galectins affect endosomal escape of antisense oligonucleotides after Stabilin-mediated endocytosis.Molecular therapy. Nucleic acids · 2023Article
- Targeted Lymphoma Therapy Using a Gold Nanoframework-Based Drug Delivery System.ACS applied materials & interfaces · 2023Article
- Hyaluronan Receptors as Mediators and Modulators of the Tumor Microenvironment.Advanced healthcare materials · 2023Review
- Review
- Systemic Glycosaminoglycan Clearance by HARE/Stabilin-2 Activates Intracellular Signaling.Cells · 2020Review
- Role of the Hyaluronan Receptor, Stabilin-2/HARE, in Health and Disease.International journal of molecular sciences · 2020Review
- Development and application of hyaluronic acid in tumor targeting drug delivery.Acta pharmaceutica Sinica. B · 2019Review
- Heparin Differentially Impacts Gene Expression of Stromal Cells from Various Tissues.Scientific reports · 2019Article
- The endothelial cell receptor stabilin-2 regulates VWF-FVIII complex half-life and immunogenicity.The Journal of clinical investigation · 2018Article
- Fascinating Fasciclins: A Surprisingly Widespread Family of Proteins that Mediate Interactions between the Cell Exterior and the Cell Surface.International journal of molecular sciences · 2018Review
- What is special about 200 kDa hyaluronan that activates hyaluronan receptor signaling?Glycobiology · 2017Article
- HYAL-2-WWOX-SMAD4 Signaling in Cell Death and Anticancer Response.Frontiers in cell and developmental biology · 2016Review
- Activation of ERK and NF-κB during HARE-Mediated Heparin Uptake Require Only One of the Four Endocytic Motifs.PloS one · 2016Article
- Lysoplex: An efficient toolkit to detect DNA sequence variations in the autophagy-lysosomal pathway.Autophagy · 2015Article
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2 authors at 1 institution in 1 country.
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Abstract
The human hyaluronan (HA) receptor for endocytosis (HARE; the 190-kDa C terminus of Stab2) is a major clearance receptor for multiple circulating ligands including HA, heparin (Hep), acetylated LDL (AcLDL), dermatan sulfate (DS), apoptotic debris, and chondroitin sulfate types A, C, D, and E. We previously found that HARE contains an N-glycan in the HA binding Link domain (at Asn(2280)), and cells expressing membrane-bound HARE(N2280A) bind and endocytose HA normally (Harris, E. N., Parry, S., Sutton-Smith, M., Pandey, M. S., Panico, M., Morris, H. R., Haslam, S. M., Dell, A., and Weigel, P. H. (2010) Glycobiology 20, 991-1001). Also, NF-κB-mediated signaling is activated by HARE-mediated endocytosis of HA, Hep, AcLDL, or DS but not by chondroitin sulfates (Pandey, M. S., and Weigel, P. H. (2014) J. Biol. Chem. 289, 1756-1767). Here we investigated the role of Link N-glycans in ligand uptake and NF-κB and ERK1/2 signaling. HA·HARE-mediated ERK1/2 activation was HA size- dependent, as found for NF-κB activation. HARE(N2280A) cells internalized HA, Hep, AcLDL, and DS normally. No ERK1/2 activation occurred during HA endocytosis by HARE(N2280A) cells, but activation did occur with Hep. Dual-luciferase recorder assays showed that NF-κB-mediated gene expression occurred normally in HARE(N2280A) cells endocytosing Hep, AcLDL, or DS but did not occur with HA. Activation of NF-κB by endogenous degradation of IκB-α was observed for HARE(N2280A) cells endocytosing Hep, AcLDL, or DS but not HA. We conclude that a Link domain complex N-glycan is required specifically for HARE·HA-mediated activation of ERK1/2 and NF-κB-mediated gene expression and that this initial activation mechanism is different from and independent of the initial mechanisms for HARE-mediated signaling in response to Hep, AcLDL, or DS uptake.
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