Atherobesity - DFG KFO 152 "Fett und Gefäß"

Subproject 5: Atherobesity: Molecular Mechanisms

Principal Investigator:

 

Prof. Dr. Annette G. Beck-Sickinger    
Institute of Biochemistry
Faculty of Biosciences, Pharmacy and Psychology
 
Universität Leipzig  
Brüderstraße 43  
04103 Leipzig   
Phone: 0341/ 97 36900  
Fax: 0341/ 97 36909  
beck-sickinger@uni-leipzig.de  

 

Summary of the Subproject:

In this project, the function of clinically relevant insulin modulating adipokines will be characterized on a molecular level. The molecular mechanisms of the interaction of the adipokine adiponectin with its receptor will be analyzed. Accordingly, we established a very efficient expression system as well as a novel read-out system for signal transduction. We identified casein kinase II as an important intracellular signalling molecule and characterized receptor dimers. Furthermore, molecular mechanisms of ligand binding will be investigated by producing and testing receptor mutants and variations of adiponectin. Subsequently, we are going to investigate the molecular mechanisms of ligand binding and clarify especially the role of the receptor N-terminus.
The second protein we are interested in is vaspin. We were able to produce vaspin and will use it to clarify the biochemical mechanism and identify target molecules. Additionally we will make it available for the clinical research group for specific experiments and mouse models. In the second funding period, we want to investigate a recently discovered adipokine: chemerin. Chemerin belongs to the class of adipokines that activate G-Protein coupled receptors. We are going to investigate the expression, structure-activity-relationships and signal transduction mechanisms.

Publications:

  1. Deckert C, Heiker JT, Beck-Sickinger AG. Localization of Novel Adiponectin Receptor Constructs. J Recept Signal Transduct Res. 2006;26:647-57.
  2. Heiker JT, Wottawah CM, Juhl C, Kosel D, Mörl K, Beck-Sickinger AG. Protein kinase CK2 interacts with adiponectin receptor 1 and participates in adiponectin signalling. Cell Signal. 2009;21:936-42.
  3. Kosel D, Heiker JT, Juhl C, Deckert C, Blüher M, Mörl K, Beck-Sickinger AG . Adiponectin receptor 1 dimerisation is inhibited by adiponectin, J Cell Sci. 2010;123:1320-8.
  4. Heiker JT, Klöting N, Blüher M, Beck-Sickinger AG. Access to gram scale amounts of functional globular adiponectin from E. coli inclusion bodies by alkaline-shock solubilization. Biophys Biochem Res Comm. 2010;398:32-7.
  5. Heiker JT, Kosel D, Beck-Sickinger AG. Molecular Mechanisms of Signal Transduction via Adiponectin and Adiponectin Receptors. Biol Chemistry. 2010;39:1005-18.
  6. Klöting N, Kovacs P, Kern M, Heiker JT, Fasshauer M, Schön MR, Stumvoll M, Beck-Sickinger AG, Blüher M. Central vaspin administration acutely reduces food intake and has sustained blood glucose-lowering effects. Diabetologia. 2011;54:1819-23.
  7. Juhl C, Mörl K, Beck-Sickinger AG. Adiponectin receptor 1 interacts with both subunits of protein kinase CK2. Mol Cell Biochem. 2011;356:185-9.
  8. Schultz S, Saalbach A, Heiker JT, Meier R, Zellmann T, Simon JC, Beck-Sickinger AG. Proteolytic activation of prochemerin by kallikrein 7 breaks an ionic linkage and results in C-terminal rearrangement. Biochem J. 2013;452:271-80.
  9. Heiker JT, Klöting N, Kovacs P, Kuettner EB, Sträter N, Schultz S, Kern M, Stumvoll M, Blüher M, Beck-Sickinger AG. Vaspin inhibits kallikrein 7 by serpin mechanism. Cell Mol Life Sci. 2013;70:2569-83.
  10. Breitfeld J, Heiker JT, Böttcher Y, Schleinitz D, Tönjes A, Weidle K, Krause K, Kuettner EB, Scholz M, Kiess W, Sträter N, Beck-Sickinger AG, Stumvoll M, Körner A, Blüher M, Kovacs P. Analysis of a rare functional truncating mutation rs61757459 in vaspin (SERPINA12) on circulating vaspin levels. J Mol Med. 2013;19:1285-92.
Imprint | Contact | ©2014 Author: Prof. Dr. M. Blüher