Publications by authors named "Kristina Kurgonaite"

Many important signalling cascades operate through specialized signalling endosomes, but a corresponding mechanism has as yet not been described for hematopoietic cytokine receptors. Based on live-cell affinity measurements, we recently proposed that ligand-induced interleukin-4 receptor (IL-4R) complex formation and thus JAK/STAT pathway activation requires a local subcellular increase in receptor density. Here, we show that this concentration step is provided by the internalization of IL-4R subunits through a constitutive, Rac1-, Pak- and actin-mediated endocytosis route that causes IL-4R subunits to become enriched by about two orders of magnitude within a population of cortical endosomes.

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Article Synopsis
  • Dimerization of the Interleukin-4 receptor (IL-4R) is crucial for the JAK/STAT signaling pathway, but observing this process in living cells has been difficult.
  • A new experimental method using trisNTA dyes allows researchers to measure the formation of receptor complexes through dual-color fluorescence cross-correlation spectroscopy, confirming that dimerization occurs only when ligands bind.
  • The study found that significant receptor densities are needed for effective dimerization, and these receptors are rapidly directed to specific endosomes beneath the cell membrane, which may help enhance the signaling process by compensating for the weak binding affinities of the receptors.
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Interleukin-4 (IL-4) is an important class I cytokine involved in adaptive immunity. IL-4 binds with high affinity to the single-pass transmembrane receptor IL-4Rα. Subsequently, IL-4Rα/IL-4 is believed to engage a second receptor chain, either IL-2Rγ or IL-13Rα1, to form type I or II receptor complexes, respectively.

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Taking tissue engineering applications into clinical trials requires the development of efficient and safe protocols incorporated with effective 3-dimensional cell culturing and differentiation systems in order to develop transplantable tissues that may offer a life-line for patients in the future. Cord blood, which is perhaps the most abundant world stem cell source, has shown previously practical and ethical advantages over other stem cells sources in many research and clinical applications including regenerative medicine. We previously developed a three-step protocol for isolation, expansion and sequential neuronal differentiation of cord blood pluripotent stem cells (characterized with our unique triple immunocytochemisty scheme for Oct-4, Sox-2 and Nanog) in defined serum-free culturing conditions.

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Aims: Superficial bladder cancer is a highly recurrent disease, with progression to muscle invasiveness occurring in 15-30% of cases. Promoter hypermethylation in a panel of tumour suppressor genes involved in cell cycle control, apoptosis and DNA repair was analyzed in superficial bladder tumours in order to evaluate the suitability of epigenetic biomarkers for an earlier prediction of the aggressive course of the disease.

Method: Promoter hypermethylation in p16, RARbeta, RASSF1A, DAPK, and MGMT genes was analyzed in 58 cases with superficial bladder cancer and 2 cases with benign urological disease using methylation-specific PCR.

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