Download Development and Differentiation

CST Signaling Pathway Diagrams for
Development and Differentiation
Wnt/β-Catenin Signaling
Notch Signaling
© 2003–2015 Cell Signaling Technology, Inc.
© 2006–2015 Cell Signaling Technology, Inc.
OFF-State
ON-State
Porc
SFRP
LRP5/6
LRP5/6
p120
Frizzled
β-catenin
Dvl
ub
CYLD
CK1
Delta
Jagged
Extracellular
Space
APC
GSK-3
WTX β-catenin
Ligand-receptor
Internalization
Delta
Jagged
Notch
TM
Deltex
NEDD4
Signal
Receiving
Cell
ub
β-catenin
TAK1
TAB2
S2 Cleavage
NICD
NUMB
ub
Ubiquitin
Degradation
FBX7
α-Adaptin
Lysosomal
Degradation
Furin
S1 Cleavage
NLK
S3 Cleavage
Endosome
Golgi
ub β-catenin
γ-Secretase
Complex
Recycling
Fringe
TAB1
Nicastrin
Presenilin
APH-1
PEN-2
ADAM/
TACE
Notch
Activated
Receptor
Rac1
Proteasomal
Degradation
ub
ub
Dvl
PAR-1
Axin
Epsin
Ligand
Repositioning
ub
Naked
PP2A
β-TrCP
Inactive
Ligand
ZNRF3
α-catenin
Tankyrase
ub
Active
Ligand
Neur
or Mib
RNF43
Frizzled
CK1 GSK-3
Axin
Skp
LGR5/6
Wnt
Cadherin
Signal
Sending
Cell
R-spondins
WLS
SFRP
DKKs
WIF
Endosome
O-Fut
ER
sm
opla
Cyt
asm
opl
Cyt
ICAT
leus
Nuc
HDAC
Pygo
Groucho
OFF
Chibby
BCL9 Brg1
Groucho β-catenin
β-catenin
Adhesion
MAML
SKIP
CSL
Inactive
Notch Target Genes
HES Family
Myc
p21
Cyclin D3
Active
Hedgehog Signaling
© 2006–2015 Cell Signaling Technology, Inc.
Hh
Skn
Pit1
FoxO
FoxO
Migration
HAT
KDM5A
SKIP
CSL
Snail1
Target Genes:
Myc, Cyclin D1,
TCF-1, PPAR-δ,
MMP-7, Axin-2,
CD44, etc.
HDAC
Hesx1
TAZ
NLK
β-catenin
CBP
LEF1/TCF1
TCF3
CtBP1 CIR HDAC
KDM5A
SMRT SHARP
leus
Nuc
ER/Golgi
HhN
Hh Secreting Cell
Mammalian
Ligands:
DISP1
Hippo Signaling
Ihh
© 2010–2015 Cell Signaling Technology, Inc.
Tight Junction
?
ZO-2 YAP/TAZ
AMOT
YAP/TAZ
?
Gα12/13
KIBRA
FRMD
Merlin
Adherens Junction
α-catenin
YAP
LKB1
Rho
AMOT
SMO
Proteasome
Nucleus
Off-State
TGF-β Ligands:
TGF-βs, Activins, Nodals
mDia
PAK
ROCK
Cy
to
YAP/TAZ
Smad
p73
TEAD1-4
TEAD1-4
Nu
cle
us
YAP/TAZ
RUNX
pla
s
PI3K
Cofilin
Transcription
JNK
p38
Smad2/3 Smad4
mTOR
Actin Polymerization
Stress Fibers
4EBP1/2
Smurf2
NF-κB
Smad1/5/9 Smad4
Smad2/3
Cofilin
Smad1/5/9
p70 S6K
Actin Polymerization
Stress Fibers
asm
opl
Angiogenesis Signaling in Tumor Neovascularization
Cyt
us
cle
Nu
© 2008–2015 Cell Signaling Technology, Inc.
Endothelial
Cell
p38
Smurf1
Cell Adhesion
Pericyte
TAK1
LIMK
Smad4
TAK1
Akt
Smad6/7
Smad1/5/9
Smad2/3
PP2A
m
Smurf1
Erk1/2
Smurf2 Smad7
Type II Receptor
Smad1/5/9
Smad7
USP4/11/15
Par6
c-Abl
LIMK
Ras
TMEPAI
TRAF4/6
PKC
MLC
SOS
SARA
Smad2/3
Rac/
Cdc42
RhoA
BMP Ligands:
BMP-2, -4, -7, MIS
Type I Receptor
Shc GRB2
ASPP2
YAP/TAZ
Nucleus
On-State
Type I Receptor
Type II Receptor
PP1
β-TrCP
VGL4
Cytoplasm
AMOT
YAP
GLI 1/2-Act
© 2003–2015 Cell Signaling Technology, Inc.
LATS1/2
YAP/TAZ
WBP2
YAP/TAZ
Cyclin D, Cyclin E,
Myc, GLI1, PTCH1,
PTCH2, Hhip1
TGF-β Signaling
F-actin
CK1
KCTD11
GLI 3-R
ITCH
14-3-3
CDON/BOC
GLI 1/2-Act
GLI 1/2 Degradation
Cytoplasm
MARK4
MOB1
Activator
Hhip1 GAS1
PTCH1
Microtubules
CDON/BOC
no transcription of
target genes
Merlin
Ajuba
Primary
Cilium
GLI 1/2/3
Repressor GLI 3-R
PP2A
Mst1/2
SAV1
14-3-3
GSK-3β
HhN
β-Arrestin
β−TrCP
CK1
Gαi/o
TAOK-1-3
SIK1-3
PTCH1
Microtubules
PKA
Gαi
GLI 1/2/3
GLI 1/2/3
Gαq/11
RASSF
KIF7
SUFU
Gαs
SMO
SUFU
PTCH2
GLI 1/2/3
?
Shh
Primary
Cilium
SUFU
Dhh
HhN
SCUBE2
KIF7
FAT4
Crb
CD44
GPCR Signaling Mechanical Signaling
Smad2/3
Basement
Membrane
Smad4 CBP
Smad2/3
Smad4 CBP
Smad1/5/9
Smad1/5/9 TF
TF
Corepressors:
Transcription Factors:
Precursor
Endothelial Cell
AP-1
RUNX
Fox
Platelet
bZIP
Sp1
IRF-7
homeodomain
nuclear receptors
bHLH
Coactivators:
c-Ski/SnoN
Evi1
HDAC4/5
TGIF
Tob (BMP only) SIP1
CBP/p300 SMIF
MSG1
ARC105
ESC Pluripotency Differentiation
© 2009–2015 Cell Signaling Technology, Inc.
PDGFR
IGF-IR
Tie2
FGFR
EPH
ROBO3
Integrins
ROBO1/2
Notch
MMPs
Neuropilin
• Growth Factors
• Cytokines
• ECM Proteases
Integrins
Tip Cell
HIF-1α
Stat3
SARA
Smad2/3
Smad1/5/9
γ−Secretase
PP2A
PI3K
MEK1/2
Target Genes
Frizzled
Gαq/o
Ras/
Raf
Ets2
BMP
Wnt
LRP
VEGFR2
Tie2
TGF-β/Activin/Nodal
FGFR
APC
Axin GSK-3
Smad2/3
Smad1/5/9
β-catenin
Smad4
Tumor Associated
Macrophage (TAM)
Erk1/2
Akt
Smad2/3 Smad4
β-catenin
NICD
Smad1/5/9 Smad4
Smad1/5/9
Smad2/3
OH
HIF-1α
elF4E1
OH
Akt
4EBP1
Erk1/2
PHDs
Normoxia
leus
TCFs
Erk1/2
Nuc
HIF-1β
HIF-1α
Smad2/3
β-catenin
Smad1/5/9
Oct-4
Sox2
Nanog
NICD
Gene Expression
Gene Expression
Hypoxia
• Growth Factors
• Cytokines
• ECM Proteases
Polycomb
Gene Expression
CBP/p300
HIF-1α
MMPs
m
plas
Cyto
HIF-1β
HRE
Pluripotency and Self Renewal
hESC markers:
Target Genes
Nucleus
Tumor
Tumor Cell
Cell
Oct-4
Sox2
SSEA3/4 TRA-1-60
Differentiation
Endoderm
Ectoderm
Nanog
TRA-1-81
Mesoderm
Primordial Germ Cells
Direct Stimulatory Modification
Tentative Stimulatory Modification
Translocation
Kinase
Caspase
pro-apoptotic
GTPase
Deacetylase
Angiopoietin 2
PDGF
Direct Inhibitory Modification
Tentative Inhibitory Modification
Phosphatase
Receptor
pro-survival
G-protein
Ribosomal subunit
bFGF
SLIT
Multistep Stimulatory Modification
Separation of Subunits
or Cleavage Products
Transcriptional Stimulatory
Modification
Transcription Factor
Enzyme
GAP/GEF
Acetylase
Angiopoietin 1
Ephrin
Multistep Inhibitory Modification
Joining of Subunits
Transcriptional Inhibitory
Modification
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VEGF
JNK