A5033324304- Growth Hormone and Insulin-like Growth Factors
- Metabolism, Diabetes, and Cancer
- Cancer, Hypoxia, and Metabolism
- Pancreatic function and diabetes
- Glycosylation and Glycoproteins Research
- Receptor Mechanisms and Signaling
- Nicotinic Acetylcholine Receptors Study
- Neuropeptides and Animal Physiology
- Diabetes and associated disorders
- Carbohydrate Chemistry and Synthesis
- Diet, Metabolism, and Disease
- Chemical Synthesis and Analysis
- Thyroid Disorders and Treatments
- Erythrocyte Function and Pathophysiology
- Lipid metabolism and disorders
- Biochemical and Molecular Research
- Cellular transport and secretion
- Diabetes Management and Research
- Genetic Syndromes and Imprinting
- Nitric Oxide and Endothelin Effects
- Click Chemistry and Applications
- Dialysis and Renal Disease Management
- Monoclonal and Polyclonal Antibodies Research
- Digestive system and related health
- Pluripotent Stem Cells Research
Flinders University
2015-2025
Flinders Medical Centre
2014-2023
University of South Australia
2015-2022
The University of Adelaide
2007-2016
Indiana University School of Medicine
2016
Walter and Eliza Hall Institute of Medical Research
2007
Monash University
2007
The University of Queensland
2007
Molecular Research Institute
2005
Zero to Three
2002
IGF-I is a key factor in intrauterine development and postnatal growth metabolism. The secretion of utero not dependent on GH, whereas childhood adult life, seems to be mainly controlled by as revealed from studies patients with GHRH receptor GH mutations. In 55-yr-old male, the first child consanguineous parents, presenting severe retardation, microcephaly, sensorineural deafness, we found homozygous G A nucleotide substitution gene changing valine 44 into methione. inactivating nature...
Abstract The insulin receptor (IR) lacking the alternatively spliced exon 11 (IR-A) is preferentially expressed in fetal and cancer cells. IR-A has been identified as a high-affinity for IGF-II but not IGF-I, which it binds with substantially lower affinity. Several cell types that express also overexpress IGF-II, suggesting possible autocrine proliferative loop. To determine regions of IGF-I responsible this differential affinity, chimeras were made where C D domains exchanged between...
Insulin-like growth factor binding proteins (IGFBP-1 to -6) bind insulin-like factors-I and -II (IGF-I IGF-II) with high affinity. These maintain IGFs in the circulation direct them target tissues, where they promote cell growth, proliferation, differentiation, survival via type 1 IGF receptor. IGFBPs also interact many other molecules, which not only influence their modulation of action but mediate IGF-independent activities that regulate processes such as migration apoptosis by modulating...
Human type 1 insulin-like growth factor receptor is a homodimeric tyrosine kinase that signals into pathways directing normal cellular growth, differentiation and proliferation, with aberrant signalling implicated in cancer. Insulin-like binding understood to relax conformational restraints within the homodimer, initiating transphosphorylation of domains. However, no three-dimensional structures exist for ectodomain inform atomic-level understanding these events. Here, we present crystal apo...
The fish-hunting marine cone snail Conus geographus uses a specialized venom insulin to induce hypoglycemic shock in its prey. We recently showed that this insulin, Con-Ins G1, has unique characteristics relevant the design of new therapeutics. Here, we show snails provide rich source minimized ligands vertebrate receptor. Insulins from C. , tulipa and kinoshitai exhibit diverse sequences, yet all bind activate human Molecular dynamics reveal modes action are distinct any other insulins...
Monomers of the insulin receptor and type 1 insulin-like growth factor (IGF-1R) can combine stochastically to form heterodimeric hybrid receptors. These receptors display ligand binding signaling properties that differ from those homodimeric Here, we describe cryoelectron microscopy structure such a in complex with I (IGF-I). The (ca. 3.7 Å resolution) displays single IGF-I ligand, bound similar fashion seen for IGFs IGF-1R. engages first leucine-rich-repeat domain cysteine-rich region...
The insulin-like growth factors (insulin-like factor I [IGF-I] and IGF-II) exert important effects on growth, development, differentiation through the IGF-I receptor (IGF-IR) transmembrane tyrosine kinase. insulin (IR) is structurally related to IGF-IR, at high concentrations, IGFs can also activate IR, in spite of their generally low affinity for latter. Two mechanisms that facilitate cross talk between IGF ligands IR physiological concentrations have been described. first these existence...
Background Insulin-like growth factor-II (IGF-II) promotes cell proliferation and survival plays an important role in normal fetal development placental function. IGF-II binds both the insulin-like factor receptor (IGF-1R) insulin isoform A (IR-A) with high affinity. Interestingly IR-A are often upregulated cancer acts via receptors to promote proliferation. There is relatively little known about mechanism of ligand induced activation (IR) IGF-1R. The recently solved IR structure reveals a...
Abstract Chemical synthesis of peptides can allow the option sequential formation multiple cysteines through exploitation judiciously chosen regioselective thiol‐protecting groups. We report use 2‐nitroveratryl (oNv) as a new orthogonal group that be cleaved by photolysis under ambient conditions. In combination with complementary S‐pyridinesulfenyl activation, disulfide bonds are formed rapidly in situ. The preparation Fmoc‐Cys(oNv)‐OH is described together its for solid‐phase complex...
The objective of this study was to employ genetically engineered IGF-II analogs establish which receptor(s) mediate the stemness promoting actions on mouse subventricular zone neural precursors. Neural precursors from were propagated in vitro culture medium supplemented with analogs. Cell growth and identity analyzed using sphere generation further by flow cytometry. F19A, an analog that does not bind IGF-2R, stimulated increase proportion stem cells (NSCs) while decreasing later stage...
Glycosylation is an accepted strategy to improve the therapeutic value of peptide and protein drugs. Insulin its analogues are life-saving drugs for all type I 30% II diabetic patients. However, they can readily form fibrils which a significant problem especially their use in insulin pumps. Because solubilizing hydration effects sugars, it was thought that glycosylation could inhibit fibril formation lead more stable formulation. Since enzymatic results heterogeneous products, we developed...
Abstract Despite recent advances in the treatment of diabetes mellitus, storage insulin formulations at 4 °C is still necessary to minimize chemical degradation. This problematic tropical regions where reliable refrigeration not ubiquitous. Some degradation byproducts are caused by disulfide shuffling cystine that leads covalently bonded oligomers. Consequently we examined utility non‐reducible isostere, cystathionine, within A‐chain. Reported herein an efficient method for forming this...
Human type 1 insulin-like growth factor receptor (IGF-1R) signals chiefly in response to the binding of I. Relatively little is known about role II signaling via IGF-1R, despite affinity for IGF-1R being within an order magnitude that Here, we describe cryoelectron microscopy structure bound a leucine-zipper-stabilized ectodomain, determined two conformations maximum average resolution 3.2 Å. The differ relative separation their respective points membrane entry, and comparison with I reveals...
We have investigated which region(s) of bovine insulin-like growth factor binding protein-2 (bIGFBP-2) interact with factors (IGFs) using C-terminally truncated forms bIGFBP-2. Initially to aid in mutant design, we defined the disulfide bonding pattern bIGFBP-2 C-terminal region enzymatic digestion. The is Cys186-Cys220, Cys231-Cys242, and Cys244-Cys265. In addition, cyanogen bromide cleavage revealed that N- cysteine-rich domains were not linked by bonds. Taking into consideration,...