The catalytically inactive mitogen-activated protein (MAP) kinase phosphatase， MK-STYX (MAPK (mitogen-activated protein kinase) phosphoserine/threonine/tyrosine-binding protein) interacts with the stress granule nucleator G3BP-1 (Ras-GAP (GTPase-activating protein) SH3 (Src homology 3) domain-binding protein-1)， and decreases stress granule (stalled mRNA) formation. Histone deacetylase isoform 6 (HDAC6) also binds G3BP-1 and serves as a major component of stress granules. The discovery that MK-STYX and HDAC6 both interact with G3BP-1 led us to investigate the effects of MK-STYX on HDAC6 dynamics. In control HEK/293 cells， HDAC6 was cytosolic， as expected， and formed aggregates under conditions of stress. In contrast， in cells overexpressing MK-STYX， HDAC6 was both nuclear and cytosolic and the number of stress-induced aggregates significantly decreased. Immunoblots showed that MK-STYX decreases HDAC6 serine phosphorylation， protein tyrosine phosphorylation， and lysine acetylation. HDAC6 is known to regulate microtubule dynamics to form aggregates. MK-STYX did not affect the organization of microtubules， but did affect their post-translational modification. Tubulin acetylation was increased in the presence of MK-STYX. In addition， the detyrosination of tubulin was significantly increased in the presence of MK-STYX. These findings show that MK-STYX decreases the number of HDAC6-containing aggregates and alters their localization， sustains microtubule acetylation， and increases detyrosination of microtubules， implicating MK-STYX as a signaling molecule in HDAC6 activity.