Life Sciences Commons^™

Structure–Function Studies Of The Yeast Saccharomyces Cerevisiae Α–Mating Factor Pheromone Receptor Ste2p, Ayça Akal–Strader

Doctoral Dissertations

G protein–coupled receptors (GPCRs) are seven transmembrane domain cell surface proteins that respond to a variety of environmental cues. Response of these receptors to their cognate stimuli on the extracellular region of the cell results in a concurrent activation of a complex series of intracellular signaling pathways that prepare the cell for the required adjustments through regulation of gene expression levels. Participation of GPCRs in such intricate signal transduction pathways renders them important players in human diseases. The GPCR family of proteins therefore represents one of the largest classes of proteins to be targeted in the development of drug design …

Central Role For Liver X Receptor In Insulin-Mediated Activation Of Srebp-1c Transcription And Stimulation Of Fatty Acid Synthesis In Liver., Guoxun Chen

Nutrition Publications and Other Works

Transcription of the gene encoding sterol regulatory element-binding protein 1c (SREBP-1c) is known to be activated by insulin in the liver. The resultant SREBP-1c protein activates transcription of the genes required for fatty acid synthesis. Here, we use SREBP-1c promoter reporter constructs to dissect the mechanism of insulin activation in freshly isolated rat hepatocytes. The data show that a complete insulin response (increase of 6- to 11-fold) requires two binding sites for liver X receptors (LXRs), which are nuclear receptors that are activated by oxygenated sterols. Disruption of these binding sites did not lower basal transcription but severely reduced the …

Liver-Specific Expression Of The Agouti Gene In Transgenic Mice Promotes Liver Carcinogenesis In The Absence Of Obesity And Diabetes, Alexander I. Kuklin, Randall L. Mynatt, Mitchell L. Klebig, Laura L. Kiefer, William O. Wilkison, Richard P. Woychik, Edward J. Michaud

Faculty Publications and Other Works -- Biochemistry, Cellular and Molecular Biology

Background

The agouti protein is a paracrine factor that is normally present in the skin of many species of mammals. Agouti regulates the switch between black and yellow hair pigmentation by signalling through the melanocortin 1 receptor (Mc1r) on melanocytes. Lethal yellow (A^y) and viable yellow (A^vy) are dominant regulatory mutations in the mouse agouti gene that cause the wild-type protein to be produced at abnormally high levels throughout the body. Mice harboring these mutations exhibit a pleiotropic syndrome characterized by yellow coat color, obesity, hyperglycemia, hyperinsulinemia, and increased susceptibility to hyperplasia and carcinogenesis …

Localizing Ligand Binding Sites Using Overlapping Recombinant Polypeptide Sequences Of Vitronectin, Jodi L. Watson

Masters Theses

Vitronectin is a glycoprotein involved in many cellular processes including blood coagulation, fibrinolysis, and cell/matrix binding. It interacts with a number of macromolecules including heparin, PAI-1, and the thrombin-antithrombin complex. We have studied the interaction of full-length vitronectin and the thrombin-antithrombin complex using a Far Western method. To localize the recognition site for thrombin-antithrombin binding to vitronectin, sequences for eight overlapping recombinant polypeptide sequences of vitronectin (spanning all 459 amino acids) were cloned into the pET system. Expression in BL21(DE3)pLysS Escherichia coli has been achieved for seven of the eight 100 amino acid fragments. Seven polypeptides (amino acids 1-100, 51-150, …