부산대학교 도서관

The pseudophosphatase MK- STYX (mitogen-activated protein kinase phosphoserine/threonine/tyrosine-binding protein) has been implicated in the stress response pathway. The expression of MK- STYX inhibits the assembly of stress granules, which are cytoplasmic storage sites for mRNA that form as a protective mechanism against stressors such as heat shock, UV irradiation and hypoxia. Furthermore, MK- STYX interacts with a key component of stress granules: G3 BP-1 ( Ras- GTPase activating protein SH3 domain binding protein-1). Because G3 BP-1 dephosphorylation at Ser149 induces stress granule assembly, we initially hypothesized that the inhibition of stress granules by MK- STYX was G3 BP-1 phosphorylation-dependent. However, in the present study, using MK- STYX constructs and G3 BP-1 phosphomimetic or nonphosphorylatable mutants, we show that MK- STYX inhibits stress granule formation independently of G3 BP-1 phosphorylation at Ser149. The introduction of point mutations at the 'active site' of MK- STYX that convert serine and phenylalanine to histidine and cysteine, respectively, is sufficient to generate an active enzyme. In separate experiments, we show that this active mutant, MK- STYXactive, has opposite effects to wild-type MK- STYK. Not only does MK- STYXactive induce stress granules, but also it has the capacity to dephosphorylate G3 BP-1. Taken together, these results provide evidence that the pseudophosphatase MK- STYX plays a key role in the cellular response to stress. [ABSTRACT FROM AUTHOR]