A5023620662- Protein Kinase Regulation and GTPase Signaling
- Metabolism, Diabetes, and Cancer
- Clinical Laboratory Practices and Quality Control
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Pancreatic function and diabetes
- Lipoproteins and Cardiovascular Health
- Computational Drug Discovery Methods
- Health and Medical Research Impacts
- Adrenal Hormones and Disorders
- Glycosylation and Glycoproteins Research
- HIV-related health complications and treatments
- Hormonal Regulation and Hypertension
- Vitamin D Research Studies
- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Monoclonal and Polyclonal Antibodies Research
- Cancer therapeutics and mechanisms
- Diabetes Management and Research
- Reproductive System and Pregnancy
- Advanced Proteomics Techniques and Applications
- Primary Care and Health Outcomes
- RNA Research and Splicing
- Artificial Intelligence in Healthcare and Education
- Vitamin C and Antioxidants Research
University of Pretoria
2016-2025
National Health Laboratory Service
2016-2025
University of Cape Town
2016-2025
Genomics (United Kingdom)
2019-2021
Istituto Giannina Gaslini
2021
Narayana Dental College and Hospital
2021
Hospital San Juan de la Cruz
2021
Çankırı Karatekin University
2021
Haukeland University Hospital
2021
Institute for Transfusion Medicine
2019
We have utilized the yeast two-hybrid system to identify proteins that interact with cytoplasmic domain of insulin receptor. identified a human cDNA is splice variant GRB10 homolog GRB-IR, which we term GRB10/IR-SV1 (for GRB10/GRB-IR 1). The protein encoded by contains an SH2 and pleckstrin homology domain. Cloning full-length revealed predicted coding sequence was similar mouse protein, although contained 80-amino acid deletion. GRB-IR such intact distinct amino terminus. interaction...
Vitamin D and its metabolites exert anti-cancer properties in various cancers; however, their effects on cervical cancer remain largely unexplored. To investigate this gap, we exposed HeLa adenocarcinoma cells to physiological the growth inhibition 20% (GI20) concentration of 25-hydroxycholecalciferol, precursor hormone active 1,25-dihydroxycholecalciferol. We then assessed impact cell health, expression genes proteins involved activation catabolism vitamin at cellular level by autocrine...
Abstract Factitiously low sodium estimations are a hazard in most modern clinical laboratories. Most high-throughput analyzers use indirect ion-selective electrodes to estimate electrolyte concentrations serum samples. This analysis is preceded by dilution step of the sample. If water concentration altered presence increased lipid or protein, and subsequent calculation analyzer results falsely value. places patients at risk, particularly if factitious result acted upon physician. In this...
The APS adapter protein is rapidly tyrosine‐phosphorylated following insulin stimulation. In insulin‐stimulated 3T3‐L1 adipocytes, co‐precipitated with phosphorylated c‐Cbl. CHO.T‐APS cells overexpressing the receptor and APS, c‐Cbl but not in CHO.T which do express APS. APS‐mediated recruitment of to led rapid ubiquitination β‐subunit parental cells. These results suggest that function facilitate coupling order catalyse initiation internalisation or degradation.
We identified SH2-Bα as an insulin-receptor-binding protein based on interaction screening in yeast hybrid systems and co-precipitation cells. contains pleckstrin-homology (‘PH’) Src homology 2 (SH2) domains is closely related to APS (adapter with a PH domain SH2 domain) lnk, adapter proteins first lymphocytes. ubiquitously expressed present rat epididymal adipose tissue, liver skeletal muscle, physiological sites of insulin action. On SDS/PAGE, migrates at molecular mass 98 kDa, although...
Abstract Factitiously low sodium estimations are a hazard in most modern clinical laboratories. Most high-throughput analyzers use indirect ion-selective electrodes to estimate electrolyte concentrations serum samples. This analysis is preceded by dilution step of the sample. If water concentration altered presence increased lipid or protein, and subsequent calculation analyzer results falsely value. places patients at risk, particularly if factitious result acted upon physician. In this...
Elevated glucose concentrations have been reported to inhibit insulin receptor kinase activity. We studied the effects of high on action in Rat1 fibroblasts transfected with wild-type human (HIRcB) and a truncated lacking COOH-terminal 43 amino acids (delta CT). In both cell lines, 25 mM impaired substrate-1 phosphorylation by 34%, but IGF-1 was unaffected. Phosphatidylinositol 3-kinase activity bromodeoxyuridine uptake were decreased 85 35%, respectively. This reversed coincubation protein...
The phosphorylation state of pp125 focal adhesion kinase in response to insulin was examined parental and transfected Rat-1 fibroblasts expressing both wild-type (HIRc cells) mutant human receptor cDNAs lacking the C-terminal twin tyrosine sites (YF2 or a deletion distal 43 amino acids β-subunit (ΔCT cells). In HIRc cells stimulated dephosphorylation fak, whereas IGF-I did not. contrast, fak unchanged YF2 ΔCT cell lines insulin. Analysis supernatants revealed that only one component major Mr...
APS (adapter protein with Pleckstrin homology and Src 2 domains) is recruited by the autophosphorylated insulin receptor essential for Glut4 translocation. Although both CAP (c-Cbl-associated protein) interact c-Cbl during signaling, relative importance of each in recruiting has not been clear. We performed a side-by-side comparison ectopic expression or 2-Bα (SH2-Bα) Chinese hamster ovary (CHO) cells. In cells co-expressing CAP, without APS, no association could be detected...
The APS adapter protein plays a pivotal role in coupling the insulin receptor to CAP and c-Cbl phosphatidylinositol 3-kinase-independent pathway of insulin-stimulated glucose transport. Yeast two-hybrid screening 3T3-L1 adipocyte library using as bait identified 418-amino acid ankyrin SOCS (suppressor cytokine signaling) box Asb6 an interactor. is orphan member larger family Asb proteins that are ubiquitously expressed. However, expression appears be restricted adipose tissue. was...
The rapidly increasing rate of antibiotic resistance is great concern. Approximately two million deaths result annually from bacterial infections worldwide. Therefore, there a paramount requirement to develop innovative and novel antibacterial agents with new mechanisms action activity against resistant strains. For this purpose, set benzothiazole N-phenylpyrrolamides derivatives reported as DNA Gyrase B (GyrB) inhibitors were collected the literature docked inside receptor cavity (PDB ID:...
Abstract Objectives Low-density lipoprotein cholesterol (LDL-C) estimation is critical for risk classification, prevention and treatment of atherosclerotic cardiovascular disease (ASCVD). Predictive equations direct LDL-C are used. We investigated the comparability between Martin/Hopkins, Sampson, Friedewald eight other predictive on two analysers, to determine whether equation or analyser influences predicted result. Methods In unpaired datasets, 9,995 lipid profiles were analysed by Abbott...
Worldwide, comprehensive newborn screening (NBS) now includes a clinical examination at birth, hearing screening, pulse oximetry measurement for congenital heart defects, and biochemical to identify disorders early in life, preventing irreversible damage, mortality enhancing overall health outcomes. This article provides overview of NBS South Africa, outlining the history, current status, future plans expansion. In is fragmented, with some investigations included neonatal assessments....
APS (adapter protein with a PH and SH2 domain) is the newest member of family tyrosine kinase adapter proteins including SH2-B Lnk. We previously identified as an insulin-receptor-binding substrate [Kotani, Wilden Pillay (1998) Biochem J. 335, 103-109]. Here we show that interacts insulin receptor activation loop through its domain stimulates tyrosine-phosphorylation APS. Furthermore, phosphorylation activation-loop residues 1158 1162 are required for this interaction.
We have demonstrated previously that dexamethasone treatment of HepG2 cells caused an enhancement insulin's metabolic effects (Kosaki, A., and Webster, N. J.(1993) J. Biol. Chem. 268, 21990-21996). This correlated with increased expression the mRNA encoding B isoform insulin receptor (IR).In present study, we in addition insulin-stimulated immediate-early gene (c-fos egr-1). Dexamethasone increase vivo IR autophosphorylation substrate-1 (IRS-1) phosphorylation both early events signaling...
Adapter protein with a pleckstrin homology (PH) and an Src 2 (SH2) domain (APS) SH2-B are adapter proteins substrates that interact the activation loop of insulin-receptor (IR) kinase. These homologous share substantial sequence similarity. We previously showed [Ahmed, Smith Pillay, FEBS Lett. 475, 31-34], for first time, insulin-stimulated phosphorylation APS led to interaction c-Cbl in 3T3-L1 adipocytes transfected Chinese-hamster ovary (CHO) cells. In present study, we find insulin...
Preclinical studies show that the anticancer actions of vitamin D metabolites are mediated by apoptosis, inhibition cell proliferation and induction cycle arrest. Cervical cancer cells express an autocrine metabolising system (VDMS) comprised a receptor, catabolic enzyme (CYP24A1), activating 25-hydroxycholecalciferol (25(OH)D3), CYP27B1. We assessed effects 25(OH)D3 at clinically relevant concentrations on cervical squamous line, SiHa. evaluated health parameters (cell count, viability,...