Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.11.2 (
PDK1
)
2,238
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
In three-dimensional matrices cancer cells move with a rounded, amoeboid morphology that is controlled by ROCK-dependent contraction of acto-myosin. In this study, we show that
PDK1
is required for phosphorylation of myosin light chain and cell motility, both on deformable gels and in vivo. Depletion of
PDK1
alters the localization of ROCK1 and reduces its ability to drive cortical acto-myosin contraction. This form of ROCK1 regulation does not require
PDK1
kinase activity, but instead involves direct binding of
PDK1
to ROCK1 at the plasma membrane;
PDK1
competes directly with
RhoE
for binding to ROCK1. In the absence of
PDK1
, negative regulation by
RhoE
predominates, causing reduced acto-myosin contractility and motility. This work uncovers a novel non-catalytic role for
PDK1
in regulating cortical acto-myosin and cell motility.
...
PMID:PDK1 regulates cancer cell motility by antagonising inhibition of ROCK1 by RhoE. 1820 40
