dictyNews
Electronic Edition
Volume 45, number 18
July 12, 2019

Please submit abstracts of your papers as soon as they have been
accepted for publication by sending them to [log in to unmask]
or by using the form at
http://dictybase.org/db/cgi-bin/dictyBase/abstract_submit.

Back issues of dictyNews, the Dicty Reference database and other
useful information is available at dictyBase - http://dictybase.org.

Follow dictyBase on twitter:
http://twitter.com/dictybase


=========
Abstracts
=========


Phosphorylated Rho-GDP directly activates mTORC2 kinase towards 
AKT through dimerization with Ras-GTP to regulate cell migration

Senoo H1, Kamimura Y2, Kimura R1, Nakajima A3, Sawai S3, Sesaki H1, 
Iijima M1

1. Department of Cell Biology, Johns Hopkins University School of 
Medicine, Baltimore, MD, USA.
2. Laboratory for Cell Signaling Dynamics, Quantitative Biology Center, 
RIKEN, Suita, Japan.
3. Department of Basic Science, Graduate School of Arts and Sciences, 
University of Tokyo, Tokyo, Japan.

Correspondence to [log in to unmask]


Nature Cell Biology. 2019. 21(7):867-878

mTORC2 plays critical roles in metabolism, cell survival and actin 
cytoskeletal dynamics through the phosphorylation of AKT. Despite its 
importance to biology and medicine, it is unclear how mTORC2-mediated 
AKT phosphorylation is controlled. Here, we identify an unforeseen 
principle by which a GDP-bound form of the conserved small G protein 
Rho GTPase directly activates mTORC2 in AKT phosphorylation in social 
amoebae (Dictyostelium discoideum) cells. Using biochemical reconstitution 
with purified proteins, we demonstrate that Rho-GDP promotes AKT 
phosphorylation by assembling a supercomplex with Ras-GTP and 
mTORC2. This supercomplex formation is controlled by the chemoattractant-
induced phosphorylation of Rho-GDP at S192 by GSK-3. Furthermore, 
Rho-GDP rescues defects in both mTORC2-mediated AKT phosphorylation 
and directed cell migration in Rho-null cells in a manner dependent on 
phosphorylation of S192. Thus, in contrast to the prevailing view that the 
GDP-bound forms of G proteins are inactive, our study reveals that 
mTORC2-AKT signalling is activated by Rho-GDP.


submitted by:  Miho Iijima  [[log in to unmask]]
==============================================================
[End dictyNews, volume 45, number 18]