A5081449694- Protein Kinase Regulation and GTPase Signaling
- Receptor Mechanisms and Signaling
- Cancer-related Molecular Pathways
- Ion channel regulation and function
- Monoclonal and Polyclonal Antibodies Research
- Bioenergy crop production and management
- Ubiquitin and proteasome pathways
- RNA Research and Splicing
- Cell Adhesion Molecules Research
- Myasthenia Gravis and Thymoma
- Forest Management and Policy
- Parasites and Host Interactions
- RNA modifications and cancer
- Click Chemistry and Applications
- Ecology and Vegetation Dynamics Studies
- Autoimmune Neurological Disorders and Treatments
- Peptidase Inhibition and Analysis
- Adenosine and Purinergic Signaling
- Cancer therapeutics and mechanisms
- Neuroscience and Neuropharmacology Research
- Biofuel production and bioconversion
- Enzyme Structure and Function
- Parasite Biology and Host Interactions
- Forest Biomass Utilization and Management
- Calcium signaling and nucleotide metabolism
Medical College of Wisconsin
2014-2024
University of Wisconsin–Madison
2013-2023
Institute of Pharmacology
2016
University of Missouri
2016
Nationwide Children's Hospital
2015
Black Country Partnership NHS Foundation Trust
2014
Medical College of Wisconsin Cancer Center
2013
Great Lakes Bioenergy Research Center
2013
Kobe University
2013
Tohoku University
2013
Striational autoantibodies (StrAb), which react with elements of skeletal muscle cross-striations, occur frequently in patients thymoma associated myasthenia gravis (MG). Dissociated thymic lymphocytes from 22 72 MG secreted StrAb when cultured PWM. A high yield EBV-transformed B cell lines was established thymus, thymoma, and peripheral blood seven MG, but clones secreting arose only the three who had their sera. The monoclonal bound to bands or I human, rat, frog. One mitochondria addition...
The small GTPase Rac1 regulates many cellular processes, including cytoskeletal reorganization, cell migration, proliferation, and survival. Additionally, plays a major role in activating NF-κB-mediated transcription. Both NF-κB regulate properties of the malignant phenotype, anchorage-independent proliferation survival, metastasis, angiogenesis. Despite these findings, roles Rac1and non-small lung carcinoma, leading cause cancer deaths, have not been thoroughly investigated. Here, we...
Inhibition of adenosine receptors could reduce metastasis by enhancing prenylation-dependent signaling that promotes cell-cell adhesion.
Objective— The pleiotropic effects of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) independent cholesterol-lowering are thought to be mediated through inhibition the Rho/Rho-kinase pathway. However, we have previously demonstrated that regular-dose statins mainly Rac1 signaling pathway rather than pathway, although molecular mechanisms selective by remain elucidated. In this study, tested our hypothesis small GTP-binding protein GDP dissociation stimulator (SmgGDS)...
We observed evolutionary conservation of canonical nuclear localization signal sequences (K(K/R)<i>X</i>(K/R)) in the C-terminal polybasic regions (PBRs) some Rac and Rho isoforms. Canonical D-box (R<i>XX</i>L), which target proteins for proteasome-mediated degradation, are also evolutionarily conserved near PBRs these small GTPases. show that Rac1 PBR (PVKKRKRK) promotes accumulation, whereas RhoA (RRGKKKSG) keeps cytoplasm. A mutant protein named (pbrRhoA), replaces PBR, has greater...
The hydrolysis of endocannabinoids has profound effects on the function endocannabinoid signaling system in regulation prostate carcinoma cells. Prostate cells exhibit a wide range activity for 2-arachidonoylglycerol (2-AG), major endocannabinoid. However, enzyme(s) responsible 2-AG and their functions cancer have not been characterized. In this study, we demonstrated that fatty acid amide hydrolase (FAAH) was differentially expressed normal PC-3 cells, overexpression FAAH resulted increased...
Ras and Rho small GTPases possessing a C-terminal polybasic region (PBR) are vital signaling proteins whose misregulation can lead to cancer. Signaling by these depends on their ability bind guanine nucleotides prenylation with geranylgeranyl or farnesyl isoprenoid moiety subsequent trafficking cellular membranes. There is little previous evidence that signals restrain nonprenylated from entering the pathway, leading general belief PBR-possessing prenylated as soon they synthesized. Here, we...
Abstract Aggressive dissemination and metastasis of pancreatic ductal adenocarcinoma (PDAC) results in poor prognosis marked lethality. Rho monomeric G protein levels are increased cancer tissue. As the mechanisms underlying PDAC malignancy little understood, we investigated role for cAMP regulating regulated invasion migration cells. Treatment cells with elevating agents that activate adenylyl cyclases, forskolin, kinase A (PKA), 6‐Bnz‐cAMP, or cyclic nucleotide phosphodiesterase inhibitor...
The armadillo protein SmgGDS promotes guanine nucleotide exchange by small GTPases containing a C-terminal polybasic region (PBR), such as Rac1 and RhoA. Because the PBR resembles nuclear localization signal (NLS) sequence, we investigated transport of with or We show that has significant NLS activity when it is fused to green fluorescent (GFP) in context full-length Rac1. In contrast, RhoA very poor GFP accumulation both enhanced activation diminished mutation PBR. Conversely, interactions...
We present the first evidence that adhesion mediated by a member of cadherin gene family can be regulated G protein-coupled receptor. show activating M3 muscarinic acetylcholine receptor (mAChR) rapidly induces E-cadherin-mediated in small cell lung carcinoma (SCLC) line. This response is inhibited E-cadherin antibodies, and does not occur another SCLC line which expresses functional mAChR but reduced levels E-cadherin. Protein kinase C may involved, since phorbol 12-myristate 13-acetate...
A greater understanding of the molecular basis breast cancer metastasis will lead to identification novel therapeutic targets and better treatments. Rap1B is a small GTPase that suppresses cells by increasing cell-cell adhesion. In cancer, decrease in prenylation subsequent loss at plasma membrane decreases adhesion increases cell scattering, which promotes metastatic phenotype. Protein kinase (PKA) was recently found phosphorylate inhibit its prenylation. PKA activated G protein-coupled...
Cancer cell-derived micro-particles (MPs) play important regulatory roles on cellular and system levels. These activities are attributed in part to protein factors carried by MPs. However, recruitment strategies for sequestering certain MPs poorly understood. In the current study, using exogenous endogenously expressed phospholipid-binding probes, we investigated distribution of membrane phospholipids as a potential mechanism electrostatically enriching cationic We detected significant level...
Non-small cell lung carcinoma (NSCLC) is promoted by the increased activities of several small GTPases, including K-Ras4B, Rap1A, Rap1B, RhoC, and Rac1. SmgGDS an unusual guanine nucleotide exchange factor that activates many these thus may promote NSCLC development or progression. We report here protein levels are elevated in tumors, compared with normal tissue from same patients individuals without cancer. To characterize functions NSCLC, we tested effects silencing expression transfecting...
Mito-CP11, a mitochondria-targeted nitroxide formed by conjugating triphenylphosphonium cation to five-membered nitroxide, carboxy-proxyl (CP), has been used as superoxide dismutase (SOD) mimetic. In this study, we investigated the antiproliferative and cytotoxic properties of submicromolar levels Mito-CP11 alone in combination with fluvastatin, well known cholesterol lowering drug, breast cancer cells. but not CP or plus cationic ligand, methyl (Me-TPP+), inhibited MCF-7 cell proliferation....
Ras family small GTPases localize at the plasma membrane, where they can activate oncogenic signaling pathways. Understanding mechanisms that promote membrane localization of will aid development new therapies to inhibit signaling. We previously reported SmgGDS splice variants prenylation and trafficking containing a C-terminal polybasic region demonstrated SmgGDS-607 interacts with nonprenylated GTPases, whereas SmgGDS-558 prenylated in cells. The mechanism use differentiate between has not...
Identifying events that regulate the prenylation and localization of small GTPases will help define new strategies for therapeutic targeting these proteins in disorders such as cancer, cardiovascular disease, neurological deficits. Splice variants chaperone protein SmgGDS (encoded by RAP1GDS1) are known to trafficking GTPases. The SmgGDS-607 splice variant regulates binding preprenylated but effects GTPase RAC1 versus RAC1B not well defined. Here we report unexpected differences their...
Cytochrome P450 (CYP) epoxygenases, CYP2C8, 2C9 and 2J2 mRNA proteins, were expressed in prostate carcinoma (PC‐3, DU‐145 LNCaP) cells. 11,12‐Epoxyeicosatrienoic acid (11,12‐EET) was the major arachidonic metabolite these Blocking EET synthesis by a selective CYP epoxygenase inhibitor (N‐methylsulfonyl‐6‐(2‐propargyloxyphenyl)hexanamide [MS‐PPOH]) inhibited tonic (basal) invasion migration (motility) while exogenously added induced cell motility concentration‐dependent manner. An epidermal...