A5012292474- Renal Diseases and Glomerulopathies
- Axon Guidance and Neuronal Signaling
- Hippo pathway signaling and YAP/TAZ
- Chronic Kidney Disease and Diabetes
- Cellular transport and secretion
- Zebrafish Biomedical Research Applications
- Genetic and Kidney Cyst Diseases
- Microtubule and mitosis dynamics
- Erythrocyte Function and Pathophysiology
- Chromatography in Natural Products
- Angiogenesis and VEGF in Cancer
- Retinal Development and Disorders
- Pancreatic function and diabetes
- Complement system in diseases
- Adolescent and Pediatric Healthcare
- Pregnancy and Medication Impact
- Protein Kinase Regulation and GTPase Signaling
- Neuroscience and Neuropharmacology Research
- Renal and related cancers
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Adenosine and Purinergic Signaling
- Diabetes and associated disorders
- Endoplasmic Reticulum Stress and Disease
Massachusetts General Hospital
2009-2023
Harvard University
2009-2023
Harvard University Press
2011
Sookmyung Women's University
2003-2007
Hallym University
2001-2003
Kidney podocytes are highly differentiated epithelial cells that form interdigitating foot processes with bridging slit diaphragms (SDs) regulate renal ultrafiltration. Podocyte injury results in proteinuric kidney disease, and genetic deletion of SD-associated CD2-associated protein (CD2AP) leads to progressive failure mice humans. Here, we have shown CD2AP regulates the TGF-β1-dependent translocation dendrin from SD nucleus. Nuclear acted as a transcription factor promote expression...
Dynamin is a 96-kDa protein that has multiple oligomerization states influence its GTPase activity. A number of different dynamin effectors, including lipids, actin filaments, and SH3-domain-containing proteins, have been implicated in the regulation oligomerization, though their roles influencing studied predominantly vitro using recombinant proteins. Here, we identify higher order oligomers such as rings helices live cells fluorescence lifetime imaging microscopy (FLIM). FLIM detected GTP-...
AbstractRecent genetic studies suggest that ephrins may function in a kinase-independent Eph receptor pathway. Here we report expression of EphA8 either NIH 3T3 or HEK293 cells enhanced cell adhesion to fibronectin via α5β1- β3integrins. Interestingly, kinase-inactive mutant also markedly promoted attachment these lines. Using panel point mutants, have demonstrated kinase activity does not correlate with its ability promote fibronectin. Analysis using extracellular and intracellular domain...
Abstract ErbB2 signalling, which is amplified by EphA2 binding, an important therapeutic target for breast cancer. Despite the importance of EphA2/ErbB2 complex in promoting tumorigenesis, mechanism these receptor tyrosine kinases (RTKs) are exported from endoplasmic reticulum (ER) remains poorly understood. Here we report that PTB adaptor Anks1a specifically localized to ER on its own serine phosphorylation. Once there, acts as regulator COPII-mediated export. The ankyrin repeat domain...
Rho family GTPases, the prototypical members of which are Cdc42, Rac1, and RhoA, molecular switches best known for regulating actin cytoskeleton. In addition to canonical small large GTPase dynamin has been implicated in cytoskeleton via direct dynamin-actin interactions. The physiologic role linked maintenance kidney filtration barrier. Additionally, molecule Bis-T-23, promotes actin–dependent oligomerization thus, increases polymerization, improved renal health diverse models CKD,...
Abstract Chronic kidney diseases and acute injury are mechanistically distinct diseases. While chronic associated with podocyte injury, affects renal tubular epithelial cells. Despite these differences, a cardinal feature of both is dysregulated actin cytoskeleton. We have shown that pharmacological activation GTPase dynamin ameliorates in murine models by promoting polymerization. Here we establish dynamin’s role modulating stiffness polarity cells crosslinking filaments into branched...
Eph receptors and ephrins have been implicated in a variety of cellular processes, including morphology motility, because their ability to modulate intricate signaling networks. Here we show that the phosphotyrosine binding (PTB) domain-containing proteins AIDA-1b Odin are tightly associated with EphA8 receptor response ligand stimulation. Both belong ankyrin repeat sterile alpha motif (Anks) protein family. The PTB domain Anks family is crucial for association juxtamembrane EphA8, whereas...
This study provides evidence that treatment with preclustered ephrin A5‐Fc results in a substantial increase the stability of p110γ PI‐3 kinase associated EphA8, thereby enhancing activity and cell migration on fibronectin substrate. In contrast, co‐expression lipid kinase‐inactive mutant together EphA8 inhibits ligand‐stimulated substrate, suggesting has dominant negative effect against endogenous kinase. Significantly, tyrosine is not important for either these processes. Taken together,...
During the preparation of this manuscript, fourth row images in Figure 5C
The gene encoding the mouse EphA8 receptor tyrosine kinase has been isolated from a genomic library, and its complete structure determined. This spans approximately 28 kb consists of 17 exons. is similar to chick EphB2(Cek5) gene, except for one intron present between first two exons domain. difference may reflect an evolutionary divergence catalytic domain EphA EphB subgroup receptors. site transcription initiation mapped 19th nucleotide upstream translation start codon ATG. A feature this...
Abstract Eph receptors and ephrins are dynamically expressed in a wide range of regions the vertebrate during embryogenesis. The dorsal mesencephalon appears to be segmented into two broad demarcated by mutually exclusive expression EphA ephrinA ligands. It is considerable interest elucidate how these domains established development mesencephalon. In this study, we used transgenic approach define cis‐acting DNA regulatory elements involved anterior mesencephalon‐specific mouse ephA8 gene....
In the present study, we demonstrate that ephrin-A5 is able to induce a transient increase of MAP kinase activity in PC12 cells. However, effects on signaling pathway are about three-fold less than EGF. addition, EphA4 only Eph member expressed cells, and tyrosine phosphorylation induced by treatment consistent with magnitude longevity activation. Experiments using Ras dominant negative mutant N17Ras reveal plays pivotal role ephrin-A5-induced activation Importantly, found receptor rapidly...
Soluble urokinase plasminogen activator receptor (suPAR) is a risk factor for kidney diseases. In addition to suPAR, proteolysis of membrane-bound uPAR results in circulating D1 and D2D3 proteins. We showed that when exposed high-fat diet, transgenic mice expressing protein developed progressive disease marked by microalbuminuria, elevated serum creatinine, glomerular hypertrophy. also exhibited insulin-dependent diabetes mellitus evidenced decreased levels insulin C-peptide, impaired...
Abstract Soluble urokinase-type plasminogen activator receptor (suPAR) is a risk factor for kidney diseases. Here we report the presence of C-terminal suPAR fragment, D2D3, in patients with diabetic nephropathy. D2D3-positive human sera inhibited glucose-stimulated insulin release islets and were associated requiring therapy. D2D3 transgenic mice presented disease diabetes marked by decreased levels C-peptide, impaired secretion, pancreatic β-cell mass, high fasting glucose. fragment...