@article{SchliermannNickel2018,
  author    = {Schliermann, Anna and Nickel, Joachim},
  title     = {Unraveling the connection between fibroblast growth factor and bone morphogenetic protein signaling},
  series = {International Journal of Molecular Sciences},
  volume    = {19},
  journal   = {International Journal of Molecular Sciences},
  number    = {10},
  issn      = {1422-0067},
  doi       = {10.3390/ijms19103220},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177358},
  year      = {2018},
  abstract  = {Ontogeny of higher organisms as well the regulation of tissue homeostasis in adult individuals requires a fine-balanced interplay of regulating factors that individually trigger the fate of particular cells to either stay undifferentiated or to differentiate towards distinct tissue specific lineages. In some cases, these factors act synergistically to promote certain cellular responses, whereas in other tissues the same factors antagonize each other. However, the molecular basis of this obvious dual signaling activity is still only poorly understood. Bone morphogenetic proteins (BMPs) and fibroblast growth factors (FGFs) are two major signal protein families that have a lot in common: They are both highly preserved between different species, involved in essential cellular functions, and their ligands vastly outnumber their receptors, making extensive signal regulation necessary. In this review we discuss where and how BMP and FGF signaling cross paths. The compiled data reflect that both factors synchronously act in many tissues, and that antagonism and synergism both exist in a context-dependent manner. Therefore, by challenging a generalization of the connection between these two pathways a new chapter in BMP FGF signaling research will be introduced.},
  language  = {en}
}
@phdthesis{Gromova2007,
  author    = {Gromova, Kira V.},
  title     = {Visualization of the Smad direct signaling response to Bone Morphogenetic Protein 4 activation with FRET-based biosensors},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-25855},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2007},
  abstract  = {The Transforming Growth Factor (TGF) superfamily of cytokines and their serine/threonine kinase receptors play an important role in the regulation of cell division, differentiation, adhesion, migration, organization, and death. Smad proteins are the major intracellular signal transducers for the TGF receptor superfamily that mediate the signal from the membrane into the nucleus. Bone Morphogenetic Protein-4 (BMP-4) is a representative of the TGF superfamily, which regulates the formation of teeth, limbs and bone, and also plays a role in fracture repair. Binding of BMP-4 to its receptor stimulates phosphorylation of Smad1, which subsequently recruits Smad4. A hetero-oligomeric complex consisting of Smad1 and Smad4 then translocates into the nucleus and regulates transcription of target genes by interacting with transcription factors. Although the individual steps of the signaling cascade from the receptor to the nucleus have been identified, the exact kinetics and the rate limiting step(s) have remained elusive. Standard biochemical techniques are not suitable for resolving these issues, as they do not offer sufficiently high sensitivity and temporal resolution. In this study, advanced optical techniques were used for direct visualization of Smad signaling in live mammalian cells. Novel fluorescent biosensors were developed by fusing cyan and yellow fluorescent proteins to the signaling molecules Smad1 and Smad4. By measuring Fluorescence Resonance Energy Transfer (FRET) between the two fluorescent proteins, the kinetics of BMP/Smad signaling was unraveled. A rate-limiting delay of 2 - 5 minutes occurred between BMP receptor stimulation and Smad1 activation. A similar delay was observed in the complex formation between Smad1 and Smad4. Further experimentation indicated that the delay is dependent on the Mad homology 1 (MH1) domain of Smad1. These results give new insights into the dynamics of the BMP receptor - Smad1/4 signaling process and provide a new tool for studying Smads and for testing inhibitory drugs.},
  subject      = {FRET},
  language  = {en}
}