Full Text Journal Articles by
Author Huilan Lin

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aPC/PAR1 confers endothelial anti-apoptotic activity via a discrete, β-arrestin-2-mediated SphK1-S1PR1-Akt signaling axis.

Olivia Molinar-Inglis, Cierra A Birch, Dequina Nicholas, Lennis Orduña-Castillo, Metztli Cisneros-Aguirre, Anand Patwardhan, Buxin Chen, Neil J Grimsey, Luisa J Coronel, Huilan Lin, Patrick K Gomez Menzies, Mark A Lawson, Hemal H Patel, JoAnn Trejo,

Endothelial dysfunction is associated with vascular disease and results in disruption of endothelial barrier function and increased sensitivity to apoptosis. Currently, there are limited treatments for improving endothelial dysfunction. Activated protein C (aPC), a promising therapeutic, signals via protease-activated receptor-1 (PAR1) and mediates several cytoprotective responses, including endothelial barrier stabilization ... Read more >>

Proc Natl Acad Sci U S A (Proceedings of the National Academy of Sciences of the United States of America)
[2021, 118(49):]

Cited: 0 times

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aPC/PAR1 confers endothelial anti-apoptotic activity via a discrete β-arrestin-2 mediated SphK1-S1PR1-Akt signaling axis

Olivia Molinar-Inglis, Cierra Birch, Dequina Nicholas, Metzli Cisneros-Aguirre, Anand Patwardhan, Buxin Chen, Neil Grimsey, Patrick Gomez-Menzies, Huilan Lin, Luisa Coronel, Mark Lawson, Hemal Patel, JoAnn Trejo,

Endothelial dysfunction is associated with multiple vascular diseases and lacks effective treatments. Activated Protein C (aPC) is a promising biotherapeutic that signals via protease-activated receptor-1 (PAR1) to promote diverse cytoprotective responses, including endothelial barrier stabilization, anti-inflammatory and anti-apoptotic activities, which is facilitated by co-receptors. We showed that aPC-activated PAR1 signals ... Read more >>

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Bi-functional IgG-lysosomal enzyme fusion proteins for brain drug delivery.

Ruben J Boado, Jeff Zhiqiang Lu, Eric Ka-Wai Hui, Huilan Lin, William M Pardridge,

Most lysosomal storage disorders affect the central nervous system. However, lysosomal enzymes do not cross the blood-brain barrier (BBB), and intravenous enzyme infusion is not effective for the brain. Lysosomal enzymes can be re-engineered for BBB transport as IgG-enzyme fusion proteins, where the IgG domain is a monoclonal antibody (MAb) ... Read more >>

Sci Rep (Scientific reports)
[2019, 9(1):18632]

Cited: 4 times

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The α-arrestin ARRDC3 suppresses breast carcinoma invasion by regulating G protein-coupled receptor lysosomal sorting and signaling.

Aleena K S Arakaki, Wen-An Pan, Huilan Lin, JoAnn Trejo,

Aberrant G protein-coupled receptor (GPCR) expression and activation has been linked to tumor initiation, progression, invasion, and metastasis. However, compared with other cancer drivers, the exploitation of GPCRs as potential therapeutic targets has been largely ignored, despite the fact that GPCRs are highly druggable. Therefore, to advance the potential status ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2018, 293(9):3350-3362]

Cited: 13 times

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Insulin Receptor Antibody-α-N-Acetylglucosaminidase Fusion Protein Penetrates the Primate Blood-Brain Barrier and Reduces Glycosoaminoglycans in Sanfilippo Type B Fibroblasts.

Ruben J Boado, Jeff Zhiqiang Lu, Eric Ka-Wai Hui, Huilan Lin, William M Pardridge,

Mucopolysaccharidosis Type IIIB (MPSIIIB) is caused by mutations in the gene encoding the lysosomal enzyme, α-N-acetylglucosaminidase (NAGLU). MPSIIIB presents with severe disease of the central nervous system, but intravenous NAGLU enzyme replacement therapy has not been developed because the NAGLU enzyme does not cross the blood-brain barrier (BBB). A BBB-penetrating ... Read more >>

Mol Pharm (Molecular pharmaceutics)
[2016, 13(4):1385-1392]

Cited: 17 times

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Endosomal signaling by protease-activated receptors.

Neil Grimsey, Huilan Lin, JoAnn Trejo,

Protease-activated receptors (PARs) are a family of G protein-coupled receptors (GPCRs) that are uniquely activated by proteolysis. There are four members of the PAR family including: PAR1, PAR2, PAR3, and PAR4. PARs are expressed primarily in the cells of the vasculature and elicit cellular responses to coagulant and anticoagulant proteases. ... Read more >>

Methods Enzymol (Methods in enzymology)
[2014, 535:389-401]

Cited: 9 times

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Cofactoring and dimerization of proteinase-activated receptors.

Huilan Lin, Allen P Liu, Thomas H Smith, JoAnn Trejo,

Proteinase-activated receptors (PARs) are G protein-coupled receptors that transmit cellular responses to extracellular proteases and have important functions in vascular physiology, development, inflammation, and cancer progression. The established paradigm for PAR activation involves proteolytic cleavage of the extracellular N terminus, which reveals a new N terminus that functions as a ... Read more >>

Pharmacol Rev (Pharmacological reviews)
[2013, 65(4):1198-1213]

Cited: 50 times

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Transactivation of the PAR1-PAR2 heterodimer by thrombin elicits β-arrestin-mediated endosomal signaling.

Huilan Lin, JoAnn Trejo,

Thrombin cleaves the N terminus of PAR1, generating a new N-terminal domain that functions as a tethered ligand that binds intermolecularly to activate PAR2 in trans. The mechanisms that regulate PAR1-PAR2 heterodimer signaling and trafficking are not known. We now report that PAR1 and PAR2 form a heterodimer that exhibits ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2013, 288(16):11203-11215]

Cited: 48 times

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AP-3 regulates PAR1 ubiquitin-independent MVB/lysosomal sorting via an ALIX-mediated pathway.

Michael R Dores, May M Paing, Huilan Lin, William A Montagne, Adriano Marchese, JoAnn Trejo,

The sorting of signaling receptors within the endocytic system is important for appropriate cellular responses. After activation, receptors are trafficked to early endosomes and either recycled or sorted to lysosomes and degraded. Most receptors trafficked to lysosomes are modified with ubiquitin and recruited into an endosomal subdomain enriched in hepatocyte ... Read more >>

Mol Biol Cell (Molecular biology of the cell)
[2012, 23(18):3612-3623]

Cited: 27 times

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Genetic and biochemical analysis of high iron toxicity in yeast: iron toxicity is due to the accumulation of cytosolic iron and occurs under both aerobic and anaerobic conditions.

Huilan Lin, Liangtao Li, Xuan Jia, Diane McVey Ward, Jerry Kaplan,

Iron storage in yeast requires the activity of the vacuolar iron transporter Ccc1. Yeast with an intact CCC1 are resistant to iron toxicity, but deletion of CCC1 renders yeast susceptible to iron toxicity. We used genetic and biochemical analysis to identify suppressors of high iron toxicity in Δccc1 cells to ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2011, 286(5):3851-3862]

Cited: 45 times

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Gain-of-function mutations identify amino acids within transmembrane domains of the yeast vacuolar transporter Zrc1 that determine metal specificity.

Huilan Lin, Damali Burton, Liangtao Li, David E Warner, John D Phillips, Diane McVey Ward, Jerry Kaplan,

Cation diffusion facilitator transporters are found in all three Kingdoms of life and are involved in transporting transition metals out of the cytosol. The metals they transport include Zn2+, Co2+, Fe2+, Cd2+, Ni2+ and Mn2+; however, no single transporter transports all metals. Previously we showed that a single amino acid ... Read more >>

Biochem J (The Biochemical journal)
[2009, 422(2):273-283]

Cited: 19 times

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A single amino acid change in the yeast vacuolar metal transporters ZRC1 and COT1 alters their substrate specificity.

Huilan Lin, Attila Kumánovics, Jenifer M Nelson, David E Warner, Diane McVey Ward, Jerry Kaplan,

Iron is an essential nutrient but in excess may damage cells by generating reactive oxygen species due to Fenton reaction or by substituting for other transition metals in essential proteins. The budding yeast Saccharomyces cerevisiae detoxifies cytosolic iron by storage in the vacuole. Deletion of CCC1, which encodes the vacuolar ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2008, 283(49):33865-33873]

Cited: 16 times

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Identification of FRA1 and FRA2 as genes involved in regulating the yeast iron regulon in response to decreased mitochondrial iron-sulfur cluster synthesis.

Attila Kumánovics, Opal S Chen, Liangtao Li, Dustin Bagley, Erika M Adkins, Huilan Lin, Nin N Dingra, Caryn E Outten, Greg Keller, Dennis Winge, Diane M Ward, Jerry Kaplan,

The nature of the connection between mitochondrial Fe-S cluster synthesis and the iron-sensitive transcription factor Aft1 in regulating the expression of the iron transport system in Saccharomyces cerevisiae is not known. Using a genetic screen, we identified two novel cytosolic proteins, Fra1 and Fra2, that are part of a complex ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2008, 283(16):10276-10286]

Cited: 134 times

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