Mutual influence on PKA and GSK3 β binding sites of GSKIP

Autor: Wan-Shia Chen, 陳宛霞
Rok vydání: 2015
Druh dokumentu: 學位論文 ; thesis
Popis: 103
Glycogen synthase kinase-3β (GSK3β) is a multifunctional serine/threonine kinase involved many physiological functions, such as the metabolism of glycogen, protein kinase A (PKA), protein kinase B (PKB), protein kinase C (PKC ) and Wingless (Wnt) pathway and its specificity and functionality may be regulated by the protein-protein interaction. Previous studies have been reported that a novel GSK3 binding protein, GSK3 interaction protein (GSKIP), is able to directly interact with PKA and GSK3. Both of GSKIP and GSK3β function as an anchoring proteins due to the inhibition of GSK3β kinase activity by PKA in the cAMP-induced signaling. Recent study suggested that GSKIP and GSK3β are involved in neural development. Under H2O2-induced apoptosis, GSK3β, as an anchoring protein, negatively modulated Drp1 to inhibit the mitochondrial fragmentation to provide the neuroprotective effects. In addition, overexpressing GSKIP to repress GSK3β kinase activity in SHY5Y cells increased the accumulation of intracellular β-cetanin and enhanced cell-cycle progression, plausibly suggesting that the interaction between GSKIP, PKA and GSK3β may directly play a role on cell growth. Therefore, by yeast two hybrid system, we used different GSKIP mutants including two short form (containing 1-108 or 115-139 residues of GSKIP) to investigate whether the yeast growth are interfered by the PKA and GSK3β binding sites of GSKIP. The results showed that overexpression of GSKIP-WT interferes yeast growth but both two short segments are not. Conversely, in animal cells, overexpression of GSKIP-WT promotes cell growth but is reduced on the GSKIP mutant-expressing cells. All the results implied that both PKA and GSK3β binding sites of GSKIP is essential for regulating the growth yeast and animal cells.
Databáze: Networked Digital Library of Theses & Dissertations
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