h1

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@PHDTHESIS{Haan:61334,
      author       = {Haan, Claude},
      othercontributors = {Heinrich, Peter C.},
      title        = {{U}ntersuchungen zur gp130/{J}ak1-{I}nteraktion},
      address      = {Aachen},
      publisher    = {Publikationsserver der RWTH Aachen University},
      reportid     = {RWTH-CONV-123007},
      pages        = {IV, 83 S. : Ill., graph. Darst.},
      year         = {2000},
      note         = {Aachen, Techn. Hochsch., Diss., 2000},
      abstract     = {The common receptor subunit gp130 is essential for cellular
                      responses following stimulation with IL-6-type cytokines.
                      Signal transduction via gp130 occurs through activation of
                      constitutively associated kinases of the Janus family (Jak1,
                      Jak2 and Tyk2). Since Jak1 plays the most important role the
                      interaction of gp130 with Jak1 was investigated by means of
                      mutagenesis of both molecules. The minimal binding region of
                      Jak1 to gp130 was restricted to the membrane proximal 68
                      amino acids. W666 and Box2 were shown to be crucial for Jak
                      binding and further signal transduction. Interestingly, the
                      amino acid exchanges W652A, P671A/P672A and F676A showed
                      that Jak1 binding is necessary but not sufficient for STAT
                      activation. Amino acid exchanges were also introduced into
                      the N-terminal domain of Jak1 and the binding of Jak1 to
                      gp130 was examined using a coimmunoprecipitation assay. A
                      structure prediction model postulating a b-grasp domain in
                      Jak1 was verified using a mutagenesis aproach. Mutations
                      L80A, L80A/Y81A and Y81A/D82A induce the loss of Jak1
                      binding to gp130. These mutants are located in loop 4
                      between two b-strands in the predicted b-grasp-model
                      indicating that this region is crucial for Jak1 binding to
                      gp130. Exchange of Y107 to alanine also abrogates Jak1
                      association to the receptor and was predicted to be
                      structurally important in the b -grasp-model.},
      cin          = {100000},
      ddc          = {570},
      cid          = {$I:(DE-82)100000_20140620$},
      typ          = {PUB:(DE-HGF)11},
      urn          = {urn:nbn:de:hbz:82-opus-145},
      url          = {https://publications.rwth-aachen.de/record/61334},
}