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Transcription
factor AP-1
Runt-related
transcription
factor 1
T-cell surface
glycoprotein
CD3 zeta chain
Inositol 1,4,5-
trisphosphate
receptor type 1
Interleukin-2
Interleukin 2
(IL-2) Receptor
1-
phosphatidylinositol
4,5-
bisphosphate
phosphodiesterase
gamma-1
Nuclear factor
of activated
T-cells
Nuclear factor
of activated
T-cells
Interleukin-2
Interleukin-2
ATP-binding
cassette,
sub-family B
(MDR/TAP),
member 1
Interleukin-2
Serine/threonine-
protein
phosphatase
PP1-alpha
catalytic
subunit
Peptidyl-prolyl
cis-trans
isomerase
FKBP1A
T-cell surface
glycoprotein
CD3
TCR complex
T-cell-specific
surface
glycoprotein
CD28
Serine/threonine-
protein
phosphatase
PP1-alpha
catalytic
subunit
Nuclear factor
of activated
T-cells
Peptidyl-prolyl
cis-trans
isomerase
FKBP1A
Inositol 1,4,5-
trisphosphate
Ca
+
Ca
+
Tacrolimus
Tacrolimus
PIP(18:0/18:1(11Z))
DG(18:0/18:1(11Z)/0:0)
P
i
Calcium
Ca
+
P
i
Tacrolimus
IL-2
Promoter
TCR Signalling
mTOR signaling
pathway
Nuclear factor
NF-kappa-B p105
subunit
Activation, Differentiation
and Migration of T Cells
MHC/Antigen
An antigen presenting cell
like a dendritic cell or
antigen activates the t cell
receptor (TCR) complex,
which includes the CD3 and
CD28 receptor.
TCR Signalling leads to IP3
production which leads to
calcium levels to increase
in the cell.
Tacrolimus is taken orally
or topically and absorbed
into the blood. It enters T
cells through ABC or SLC
transporters like the ABCB1
transporter.
Tacroblimus binds to FKBP12
to form a complex which
inhibits calcineurin. It
subsequently inhibits the
dephosphorylation of of
NFAT.
NFAT is an important
transcription protein for
interleukin 2 (IL-2)
production in T cells, so a
lower concentration of NFAT
being activated leads to
lower IL-2 production.
IL-2 is released outside the
cell through vesicle
packaging in the golgi
apparatus.
IL-2 can act in an autocrine
or paracrine way once it is
in the extracellular space.
IL-2 interacts with
interleukin-2 receptor on
T-cells which leads to mTOR
signalling. Decreased IL-2
production leads to less
activation of receptors.
mTOR signalling would lead
to activation,
differentiation and
migration of T-cells, but
reduced IL-2 would lead to
decreased aforementioned
activities.
Nucleus
Endoplasmic Reticulum
Golgi Apparatus
Cytosol
Nucleus
Endoplasmic Reticulum
JUN
RUNX1
CD247
ITPR1
IL2
IL2RG
PLCG1
NFATC3
NFATC3
IL2
IL2
ABCB1
IL2
PPP1CA
FKBP1A
CD3E
TRB
CD28
PPP1CA
NFATC3
FKBP1A
Inositol 1,4,5-
trisphosphate
Calcium
Calcium
Tacrolimus
Tacrolimus
PIP(18:0/18:1(11Z))
DG(18:0/18:1(11Z)/0:0)
Phosphate
Calcium
Phosphate
Tacrolimus
IL-2
Promoter
TCR Signalling
mTOR signaling
pathway
NFKB1
JUN
RUNX1
CD247
ITPR1
IL2
IL2RG
PLCG1
NFATC3
NFATC3
IL2
IL2
ABCB1
IL2
PPP1CA
FKBP1A
CD3E
TRB
CD28
PPP1CA
NFATC3
FKBP1A
Inotp
Ca
+
Ca
+
Tacroli
Tacroli
PIP36:1
DG36:1
P
i
Ca2+
Ca
+
P
i
Tacroli
IL-2
P
TCR Sig
PW076001