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Phospholipase D in cell signaling: from a myriad of cell functions to cancer growth and metastasis.
[wiskott-aldrich syndrome]
Phospholipase
D
(
PLD
)
enzymes
play
a
double
vital
role
in
cells
:
they
maintain
the
integrity
of
cellular
membranes
and
they
participate
in
cell
signaling
including
intracellular
protein
trafficking
,
cytoskeletal
dynamics
,
cell
migration
,
and
cell
proliferation
.
The
particular
involvement
of
PLD
in
cell
migration
is
accomplished
:
(
a
)
through
the
actions
of
its
enzymatic
product
of
reaction
,
phosphatidic
acid
,
and
its
unique
shape-binding
role
on
membrane
geometry
;
(
b
)
through
a
particular
guanine
nucleotide
exchange
factor
(
GEF
)
activity
(
the
first
of
its
class
assigned
to
a
phospholipase
)
in
the
case
of
the
mammalian
isoform
PLD
2
;
and
(
c
)
through
protein-protein
interactions
with
a
wide
network
of
molecules
:
Wiskott-
Aldrich
syndrome
protein
(
WASp
)
,
Grb
2
,
ribosomal
S
6
kinase
(
S
6
K
)
,
and
Rac
2
.
Further
,
PLD
interacts
with
a
variety
of
kinases
(
PKC
,
FES
,
EGF
receptor
(
EGFR
)
,
and
JAK
3
)
that
are
activated
by
it
,
or
PLD
becomes
the
target
substrate
.
Out
of
these
myriads
of
functions
,
PLD
is
becoming
recognized
as
a
major
player
in
cell
migration
,
cell
invasion
,
and
cancer
metastasis
.
This
is
the
story
of
the
evolution
of
PLD
from
being
involved
in
a
large
number
of
seemingly
unrelated
cellular
functions
to
its
most
recent
role
in
cancer
signaling
,
a
subfield
that
is
expected
to
grow
exponentially
.
Diseases
Validation
Diseases presenting
"large number"
symptom
acute rheumatic fever
adrenal incidentaloma
allergic bronchopulmonary aspergillosis
canavan disease
coats disease
cowden syndrome
dedifferentiated liposarcoma
dracunculiasis
epidermolysis bullosa simplex
fabry disease
familial mediterranean fever
gm1 gangliosidosis
heparin-induced thrombocytopenia
hereditary cerebral hemorrhage with amyloidosis
hirschsprung disease
kindler syndrome
legionellosis
malignant atrophic papulosis
neuralgic amyotrophy
phenylketonuria
pleomorphic liposarcoma
primary effusion lymphoma
scrub typhus
severe combined immunodeficiency
triple a syndrome
waldenström macroglobulinemia
well-differentiated liposarcoma
wiskott-aldrich syndrome
wolf-hirschhorn syndrome
x-linked adrenoleukodystrophy
zellweger syndrome
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