Master of Science (M.Sc.)
Shantá D Hinton
Lizabeth A Allison
Mark H Forsyth
The intriguing protein MK-STYX [MAPK (mitogen-activated protein kinase) phospho-serine/threonine/tyrosine-binding protein] has been receiving attention because recent work has implicated it in a number of biological processes. MK-STYX is a pseudophosphatase involved in cellular stress responses, neuronal differentiation, apoptosis, and several cancers. As a pseudophosphatase, it is catalytically inactive due to mutations in its enzyme active site. However, it retains structural domains that enable it to perform protein-protein interactions. It is important to consider how exactly MK-STYX may carry out its many functions. Another multifunctional protein, known as GSK3 (glycogen synthase kinase 3) has some overlapping functions with MK-STYX so it is exciting to consider that MK-STYX may impact GSK3 to exert its cellular functions. GSK3 refers to two paralogous and homologous enzymes known as GSK3 and GSK3. These are regulated by inhibitory phosphorylation on serine 21/9 and activating phosphorylation on tyrosine 279/216 for GSK3/, respectively. Accordingly, biochemical studies were carried out to determine whether MK-STYX changed the phosphorylation at these sites, or indeed if MK-STYX changed the amount of GSK3. A multifunctional kinase like GSK3 has many physiological roles, so if MK-STYX changes regulatory phosphorylation sites or protein expression of GSK3, it was hypothesized that MK-STYX could affect GSK3 functions, and that additionally, MK-STYX could form a protein complex with GSK3 and then modulate it. Western blot analysis revealed that MK-STYX decreased serine 9 phosphorylation on GSK3, suggesting that MK-STYX activates GSK3. MK-STYX did not change serine 21 phosphorylation on GSK3. Also, MK-STYX did not affect total expression of GSK3/. Further, there was no detected interaction between MK-STYX and GSK3 as indicated by coimmunoprecipitation. Overall, this thesis suggests MK-STYX may have some regulatory role over GSK3. Further biochemical work should clarify this connection and its biological significance.
© The Author
Mattei, Andrew M., "Exploring A Connection Between MK-STYX And GSK3" (2022). Dissertations, Theses, and Masters Projects. William & Mary. Paper 1673281824.
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