Date of this Version
9-21-2015
Document Type
Article
Rights
by-nc-sa
Abstract
We have previously shown that the Dictyostelium protein phosphatase 2A regulatory subunit B56, encoded by psrA, modulates Dictyostelium cell differentiation through negatively affecting glycogen synthase kinase 3 (GSK3) function. Our follow-up research uncovered that B56 preferentially associated with GDP forms of RasC and RasD, but not with RasG in vitro, and psrA− cells displayed inefficient activation of multiple Ras species, decreased random motility, and inefficient chemotaxis toward cAMP and folic acid gradient. Surprisingly, psrA− cells displayed aberrantly high basal and poststimulus phosphorylation of Dictyostelium protein kinase B (PKB) kinase family member PKBR1 and PKB substrates. Expression of constitutively active Ras mutants or inhibition of GSK3 in psrA− cells increased activities of both PKBR1 and PKBA, but only the PKBR1 activity was increased in wild-type cells under the equivalent conditions, indicating that either B56- or GSK3-mediated suppressive mechanism is sufficient to maintain low PKBA activity, but both mechanisms are necessary for suppressing PKBR1. Finally, cells lacking RasD or RasC displayed normal PKBR1 regulation under GSK3-inhibiting conditions, indicating that RasC or RasD proteins are essential for GSK3-mediated PKBR1 inhibition. In summary, B56 constitutes inhibitory circuits for PKBA and PKBR1 and thus heavily affects Dictyostelium chemotaxis.
DOI
10.1091/mbc.E14-06-1130
Identifier
FIDC001623
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 License.
Recommended Citation
Rodriguez Pino, M., Castillo, B., Kim, B., Kim, L.W. (2015). PP2A/B56 and GSK3/Ras suppress PKB activity during Dictyostelium chemotaxis. Mol Biol Cell, 26(24):4347-57.
Rights Statement
In Copyright - Non-Commmercial Use Permitted. URI: http://rightsstatements.org/vocab/InC-NC/1.0/
This Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. In addition, no permission is required from the rights-holder(s) for non-commercial uses. For other uses you need to obtain permission from the rights-holder(s).
Comments
Originally published in Molecular Biology of the Cell.