@article{KruseShenArnoldetal.1993,
  author    = {Kruse, N. and Shen, B. J. and Arnold, S. and Tony, H. P. and M{\"u}ller, T. and Sebald, Walter},
  title     = {Two distinct functional sites of human interleukin 4 are identified by variants impaired in either receptor binding or receptor activation},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62451},
  year      = {1993},
  abstract  = {Interleukin 4 (IL-4) exerts a decisive role in the coord.ination of proteelive immune responses against parasites, particularly helminths. A disregulation of ll.r4 function is possibly involved in the genesis of allergic disease states. The search for important amino acid residues in human ll.r4 by mutational analysis of charged invariant amino acid positions identified two distinct functional sites in the 4-helix-bundle protein. Site 1 was marked by amino acid substitutions of the glutamic acid at position 9 in helix A and arginine at position 88 in helix C. Exchanges at both positions led to IL-4 variants deficient in binding to the extracellular domain of the ll.r4 receptor (IL-4ReJ. In parallel, up to 1000-fold increased concentrations of this type of variant were required to induce T -cell proliferation and B-eeil CD23 expression. Site 2 was marked by amino acid exchanges in helix D at positions 121, 124 and 125 (arginine, tyrosine and serine respectively in the wild-type).ß.A variants affected at site 2 exhibited partial agonist activity during T -cell proliferation; however, they still bound with high affinity to IL-4Rex. [The generation of an IL-4 antagonist by replacing tyrosine 124 with aspartic acid has been described before by Kruse et al. (1992) (EMBO }., 11, 3237-3244)]. These findings indicate that IL-4 functions by bind.ing IL-4Rex via site 1 which is constituted by residues on helices A and C. They further suggest that the association of a second, still undetined receptor protein with site 2 in helix D activates the receptor system and generates a transmembrane signal.},
  subject      = {Biochemie},
  language  = {en}
}
@article{SeherLaglerStuehmeretal.2017,
  author    = {Seher, Axel and Lagler, Charlotte and St{\"u}hmer, Thorsten and M{\"u}ller-Richter, Urs Dietmar Achim and K{\"u}bler, Alexander Christian and Sebald, Walter and M{\"u}ller, Thomas Dieter and Nickel, Joachim},
  title     = {Utilizing BMP-2 muteins for treatment of multiple myeloma},
  series = {PLoS ONE},
  volume    = {12},
  journal   = {PLoS ONE},
  number    = {5},
  doi       = {10.1371/journal.pone.0174884},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158144},
  pages     = {e0174884},
  year      = {2017},
  abstract  = {Multiple myeloma (MM) represents a haematological cancer characterized by the pathological hyper proliferation of antibody-producing B-lymphocytes. Patients typically suffer from kidney malfunction and skeletal disorders. In the context of MM, the transforming growth factor β (TGFβ) member Activin A was recently identified as a promoter of both accompanying symptoms. Because studies have shown that bone morphogenetic protein (BMP)-2-mediated activities are counteracted by Activin A, we analysed whether BMP2, which also binds to the Activin A receptors ActRII and ActRIIB but activates the alternative SMAD-1/5/8 pathway, can be used to antagonize Activin A activities, such as in the context of MM. Therefore three BMP2 derivatives were generated with modified binding activities for the type II (ActRIIB) and/or type I receptor (BMPRIA) showing either increased or decreased BMP2 activity. In the context of MM these BMP2 muteins show two functionalities since they act as a) an anti-proliferative/apoptotic agent against neoplastic B-cells, b) as a bone-formation promoting growth factor. The molecular basis of both activities was shown in two different cellular models to clearly rely on the properties of the investigated BMP2 muteins to compete for the binding of Activin A to the Activin type II receptors. The experimental outcome suggests new therapeutic strategies using BMP2 variants in the treatment of MM-related pathologies.},
  language  = {en}
}