Journal of Biological Chemistry
Volume 287, Issue 52, 21 December 2012, Pages 43620-43629
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Signal Transduction
Rho-associated Coiled-coil Kinase (ROCK) Protein Controls Microtubule Dynamics in a Novel Signaling Pathway That Regulates Cell Migration*

https://doi.org/10.1074/jbc.M112.394965Get rights and content
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The two members of the Rho-associated coiled-coil kinase (ROCK1 and 2) family are established regulators of actin dynamics that are involved in the regulation of the cell cycle as well as cell motility and invasion. Here, we discovered a novel signaling pathway whereby ROCK regulates microtubule (MT) acetylation via phosphorylation of the tubulin polymerization promoting protein 1 (TPPP1/p25). We show that ROCK phosphorylation of TPPP1 inhibits the interaction between TPPP1 and histone deacetylase 6 (HDAC6), which in turn results in increased HDAC6 activity followed by a decrease in MT acetylation. As a consequence, we show that TPPP1 phosphorylation by ROCK increases cell migration and invasion via modulation of cellular acetyl MT levels. We establish here that the ROCK-TPPP1-HDAC6 signaling pathway is important for the regulation of cell migration and invasion.

Cell Motility
Histone Deacetylase
Microtubules
Phosphorylation
Signaling
HDAC6
MT Acetylation
ROCK
TPPP1/p25

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*

This research was supported by grants from the National Health and Medical Research Council (NHMRC), the Australian Research Council (ARC), the Cancer Council of Victoria, and in part by the Victorian Government Operational Infrastructure Support Program. This work was also supported by a fellowship from the NHMRC (to O. B.) and by an Australian Postgraduate Award and St. Vincent's Institute Foundation Top-up Scholarship (to A. V. S.).

This article contains supplemental Fig 1.