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Involvement of Gab1 in Müller cell proliferation

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dc.contributor Graduate Program in Molecular Biology and Genetics.
dc.contributor.advisor Buğra, Kuyaş.
dc.contributor.author Dilvin Yıldırım, Hanife.
dc.date.accessioned 2023-03-16T11:25:45Z
dc.date.available 2023-03-16T11:25:45Z
dc.date.issued 2019.
dc.identifier.other BIO 2019 D56
dc.identifier.uri http://digitalarchive.boun.edu.tr/handle/123456789/15382
dc.description.abstract Müller cells, the major type of glial cells in the retina, are reactivated in response to most retinal injuries and diseases. In fish the reactivated Müller cells proliferate and transdifferentiate to make up for the lost neurons. Although in mammals, neurogenesis is not evident in situ, Müller cell proliferation can be stimulated by exogenous growth factors such as FGF2 through the activation of the Ras/ERK pathway. Previous work from our laboratory suggests that SIK2 is involved in a negative feedback mechanism of FGF2-induced Ras/ERK pathway. We propose that this process involves Gab1 phosphorylation by SIK2 at S266, which disrupts interactions of Gab1 with binding partners and downregulate proliferation. In this study, to provide further support for the role of Gab1 in this mechanism, SIK2 or Gab1 silenced MIO-M1 cells were generated by shRNA approach along with S266A mutant Gab1 transfected MIO-M1 cell line. The effects of these modulations on ERK activation and cell proliferation was investigated. The duration of ERK activation increased in both SIK2 downregulated and S266A mutant Gab1 expressing cells and higher level of proliferation was observed. Gab1 silencing led to a dramatic increase in amplitude of ERK phosphorylation in the initial phase of ERK activation but did not alter the duration of the signaling. These findings raise the possibility of dual role for Gab1 where it switches from suppressor to amplifier during the course of FGF2-induced ERK signaling.
dc.format.extent 30 cm.
dc.publisher Thesis (M.S.) - Bogazici University. Institute for Graduate Studies in Science and Engineering, 2019.
dc.subject.lcsh Protein kinases.
dc.subject.lcsh Fibroblast growth factors.
dc.title Involvement of Gab1 in Müller cell proliferation
dc.format.pages xvi, 59 leaves ;


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