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Dijital Arşivi

SIK2 involvement in dowregulation of FGF signaling through Gab1 and Raf1

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dc.contributor Graduate Program in Molecular Biology and Genetics.
dc.contributor.advisor Bilge, Kuyaş Buğra.
dc.contributor.author Sert, Yeliz Yılmaz.
dc.date.accessioned 2023-03-16T11:26:04Z
dc.date.available 2023-03-16T11:26:04Z
dc.date.issued 2011.
dc.identifier.other BIO 2011 S47
dc.identifier.uri http://digitalarchive.boun.edu.tr/handle/123456789/15441
dc.description.abstract Proliferative response of Müller cells to FGF2 is propagated via Ras/MAPK pathway, and involves rapid and transient ERK1/2 activation. Results from our laboratory implicate SIK2 in the regulation of FGF2 signaling via serine/threonine phosphorylation of pathway elements Gab1 and Raf1, on Ser266 and Ser621 respectively. We propose that these phosphorylations hamper interaction with the partners to activate downstream events. In this study to test the hypothesis, Ser266 on Gab1 and Ser621 on Raf-1 were mutated to alanine via site-directed mutagenesis. As Ser621 has been described as an autophosphorylation site, Raf-1 was also rendered kinase inactive. Wild type and mutant proteins expressed in HEK 293T cells were purified by immunoprecipitation and were used for in vitro kinase assay. Results obtained from in vitro kinase assays indicated that the mutations obliterated the phosphorylation by SIK2, thus verified that SIK2 targets these serine residues. Co-immunoprecipitation studies revealed that S266A mutation increases FGF dependent Gab1-Shp2 binding, no differences were evident in Grb2-Gab1 interaction. Therefore, it is conceivable that the Ser266 phosphorylation by SIK2 is important in transient nature of Gab1 interaction with Shp2 and might regulate FGF-dependent ERK activation. The mutation led to modest enhancement of FGF dependent proliferation in MIO-M1 cells.
dc.format.extent 30cm.
dc.publisher Thesis (M.S.) - Bogazici University. Institute for Graduate Studies in Science and Engineering, 2011.
dc.subject.lcsh Fibroblast growth factors.
dc.subject.lcsh Protein kinases.
dc.subject.lcsh Retina.
dc.title SIK2 involvement in dowregulation of FGF signaling through Gab1 and Raf1
dc.format.pages xiv, 80 leaves ;


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