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ABSTRACT
Cell motility is an essential cellular process for a variety of biological events. It requires cross-talk between the signaling and the cytoskeletal systems. Despite the recognized importance of aPKCζ for cell motility, there is little understanding of the mechanism by which aPKCζ mediates extracellular signals to the cytoskeleton. In the present study, we report that aPKCζ is required for the cellular organization of acto-non-muscle myosin II (NMII) cytoskeleton, for proper cell adhesion and directed cell migration. We show that aPKCζ mediates EGF-dependent RhoA activation and recruitment to the cell membrane. We also show that aPKCζ mediates EGF-dependent myosin light chain (MRLC) phosphorylation that is carried out by Rho-associated protein kinase (ROCK), and that aPKCζ is required for EGF-dependent phosphorylation and inhibition of the myosin phosphatase targeting subunit (MYPT). Finally, we show that aPKCζ mediates the spatial organization of the acto-NMII cytoskeleton in response to EGF stimulation. Our data suggest that aPKCζ is an essential component regulator of acto-NMII cytoskeleton organization leading to directed cell migration, and is a mediator of the EGF signal to the cytoskeleton.
Disclosure of potential conflicts of interest
No potential conflicts of interest were disclosed.
Acknowledgments
We thank Jorge Moscat (Sanford-Burnham Medical Research Institute, La Jolla) for aPKCζ wild type (control) and aPKCζ−/− cell lines.
Funding
This study was supported by the Israel Science Foundation (Grant No. 1174/12), Israel Cancer Research Foundation, and Israel Cancer Association (Grant No. 20140082). S.R. holds the Dr. Daniel G. Miller Chair in Cancer Research. I.D. was supported by the Canadian Friends of Hebrew University. D.P. was supported by the Luxemburg Foundation.
