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Cell Signaling Technology

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Direct Stimulatory Modification

Direct Inhibitory Modification

Multistep Stimulatory Modification

Multistep Inhibitory Modification

Tentative Stimulatory Modification

Tentative Inhibitory Modification

Transcriptional Inhibitory Modification

Pathway Diagram Key

Angiogenesis

VHL

Cul2Rbx1TCEB2

TCEB1

PHDs

elF4E1 4E-BP1

Erk1/2

Erk1/2

MNK

MEK1/2 Ras

S6K

mTOR

Akt PI3K

CBP/p300

HIF1α

HIF1α

HIF1β

HIF1β

HIF1α

PI3K Src

NOSAkt

FAK PLCλ

Erk1/2

Smad2/3p38 MAPK

HIF1α

HIF1α

Matrix RemodelingPAI-1

MMPCox2

OH

OH

OH

Normoxia

Nucleus

VEGFR2

VEGF

Tie2FGFR IGFR

EGFR

PDGFR-β

PDGF-BB

ROBO

SLIT

Notch

E3 Ligase Complex

Degradation

• Growth Factors• Cytokines• ECM Proteases

ExtracellularMatrix

Endothelial Cell

Pericyte

Normoxia

NormoxiaHypoxia

Angiogenesis

Blood Vessel

VascularGuidance

Cell Fate

VascularPermeability

Survival Migration ProliferationPericyteProliferation

Target GenesHRE

Basement Membrane

Cytoplasm

Pro-Angiogenic Cell

Extracellular S

pace

rev. 08/24/18rev. 08/24/18