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0:00
Hello.
I'm Reiko Sugiura
of the Laboratory
of Molecular Pharmacogenomics,
Department
of Pharmaceutical Sciences,
Kinki University.
I'd like to talk about
"MAPK Signaling Regulation
and Cancer,
Lessons from Fission Yeast."
0:17
First, I'll give you a overview
of MAPK signaling.
Second, I'll introduce
our molecular genetic approach
to identify regulators
with MAPK signaling.
Third, I'll explain
how we applied
our chemical genomic screen
to identify inhibitors
of MAPK signaling.
And finally, I'd like to discuss
the physiological
and the medical implications
of this regulation
in human diseases,
including cancers.
0:47
This is a scheme of the MAPK
signaling cascade.
This mitogen-activated
protein, kinase,
or a MAPK cascade is a highly
conserved signaling module
that is involved in various
cellular functions
including cell proliferation,
differentiation and migration.
MAPK pathways consist of
a series of
at least three kinases,
extracellular stimulus,
such as growth factors
and environmental stresses
induced
the sequential activation
of MAP kinase kinase kinase,
MAP kinase kinase
and MAP kinase.
The MAP kinase is activated
by a unique way.
MAP kinases are activated
by phosphorylation
on both the threonine
and tyrosine residues
over a conserved signature,
TxY motif within the
activation loop of the kinase.
This is carried out
by an upstream
dual-specificity
MAP kinase kinase,
which is in turn regulated
by phosphorylation
of serine and threonine
residues by a MAPKKK.
Since phosphorylation
is required
for the activation
of MAP kinases,
the phosphorylation of MAPKs
by members of the MAP kinase
phosphatase family
plays a critical role
in negative re-regulating
of MAPK signaling
and transduction pathway.
This can be achieved by serine
and threonine phosphatases,
tyrosine-specific
phosphatases
or by dual-specificity
phosphatases.
Studies in a wide
variety of modules,
from yeast to man
have demonstrated that
all three major classes
of protein phosphatases
can perform this task in vivo.
