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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
"cancer"
symptom
achondroplasia
acute rheumatic fever
adrenal incidentaloma
alpha-thalassemia
benign recurrent intrahepatic cholestasis
cadasil
canavan disease
carcinoma of the gallbladder
cholangiocarcinoma
coats disease
congenital adrenal hyperplasia
congenital diaphragmatic hernia
cowden syndrome
cushing syndrome
cutaneous mastocytosis
dedifferentiated liposarcoma
dystrophic epidermolysis bullosa
epidermolysis bullosa simplex
erdheim-chester disease
erythropoietic protoporphyria
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
familial hypocalciuric hypercalcemia
familial mediterranean fever
gm1 gangliosidosis
heparin-induced thrombocytopenia
hereditary cerebral hemorrhage with amyloidosis
hirschsprung disease
hodgkin lymphoma, classical
inclusion body myositis
junctional epidermolysis bullosa
kabuki syndrome
kallmann syndrome
kindler syndrome
lamellar ichthyosis
liposarcoma
locked-in syndrome
lymphangioleiomyomatosis
monosomy 21
neuralgic amyotrophy
oculocutaneous albinism
oligodontia
oral submucous fibrosis
papillon-lefèvre syndrome
pendred syndrome
pleomorphic liposarcoma
primary effusion lymphoma
proteus syndrome
pyomyositis
pyruvate dehydrogenase deficiency
severe combined immunodeficiency
sneddon syndrome
systemic capillary leak syndrome
triple a syndrome
von hippel-lindau disease
waldenström macroglobulinemia
well-differentiated liposarcoma
werner syndrome
wiskott-aldrich syndrome
wolf-hirschhorn syndrome
x-linked adrenoleukodystrophy
This symptom has already been validated
