Cellular Metabolism - Cell Signaling...

CST SIGNALING PATHWAY DIAGRAMS FOR

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Cellular Metabolism

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Direct Stimulatory Modification

Direct Inhibitory Modification

Multistep Stimulatory Modification

Multistep Inhibitory Modification

Tentative Stimulatory Modification

Tentative Inhibitory Modification

Separation of Subunits or Cleavage Products

Joining of Subunits

Translocation

Transcriptional Stimulatory Modification

Transcriptional Inhibitory Modification

Kinase

Phosphatase

Transcription Factor

Caspase

Receptor

Enzyme

pro-apoptotic

pro-survival

GAP/GEF

GTPase

G-protein

Acetylase

Deacetylase

Ribosomal subunit

Other RTKsα-AdrenergicReceptor

AMPKαβ γ

PFKFB3

LKB1MO25αSTRAD

Adiponectin Receptor

Leptin

PKA Ras

Rheb

PLCβ Gαq

SirT1

GS TBC1D1

ACC

CPT1Malonyl

CoA

CaMKK

HMG-CoAReductase

FIP200

TSC2TSC1

PGC1α

Insulin

SREBP-1

Fatty AcidSynthase

HSL

ATGL

Akt

B-Raf

Erk

p90RSK

PI3K

InsulinReceptor

p70S6K

4E-BP1

Beclin

mTOR GβLRaptor

ULK1

PI3KClass III

ATG13

Atg14

p300

HNF4α

TORC2/CRTC2

CREB

FoxO

HDAC7HDAC5HDAC4

CRY1

Glut4vesicle

Glut1vesicle

Sterol/IsoprenoidSynthesis

Fatty AcidOxidation

Lipolysis

Glycolysis

GlycogenSynthesis

[cAMP]

Low Glucose,Hypoxia, Ischemia,

Heat ShockAICAR

ExerciseBrain

[Ca2+]

HistamineThrombin

GlutTrafficking

Glut4Glut1

Autophagy

Lipogenesis

AMP + ADPATP

Gluconeogenesis

Glucose

Glut Translocation

Microtubules

ActinDynamics

MBS85MYPT1

TXNIP

MyosinLight

Chain2

CLIP170Tau

Cytoskeletal Signaling

Acute Regulation of M

etabolism

Transcriptional Control of Metabolism

Prot

ein

Met

abol

ism a

nd A

utop

hagy

AMPK Signaling© 2008–2015 Cell Signaling Technology, Inc.

PDHK

IDH1

IDH2

PHGDH

Ras

Ras

Ras

UCP2

ACSS2Malate

Malate

Citrate Citrate

Acetate

EpigeneticRegulation

ACL

ACC

LDHAPyruvate

Dehydrogenase

NADPH

NADPH

NADPH

NADP

NADP

NADP

Malic Enzyme

Glutaminase

Oxaloacetate

Glutamine Transporters

Glucose Transporters

Hexokinase

PFK

PKM2

Acetyl-CoA

Glutamine

OMM StabilityInhibition Cytochrome C Release

Inhibition of Apoptosis

Glutaminolysis

Acetyl-CoAPyruvate

Pyruvate

6-P-Gluconolactone

6-P-Gluconate

Amino Acidsand Lipids

Ribulose-5P

NucleotideSynthesis

FolateMetabolism

Fructose-6-P

FructoseBisphosphate

3-Phosphoglycerate

PEP

Glucose-6-P

Lactate

Serine

Glycine

KrebsCycle

VDACHexokinase

Bax

VDAC

ANTANT

α-Ketoglutarate

β-Oxidation

MEK1/2

AMPK

p53TIGAR

c-Myc

c-Myc

AMPK

c-Myc

HIF-1α

HIF-1α

SREBPLKB1

ULK1

c-Myc

Erk1/2

Akt

Akt

mTOR

NADPHNADP

NADPH

NADP

PI3K

p53

Amino Acids

Cell Proliferation

Fatty Acid Oxidation

Autophagy Fatty Acids

Fatty Acid/Lipid Synthesis

Protein Synthesis

Growth FactorsMacropinocytosis and

other scavenging pathwaysGlucose

Glycolysis

PentosePhosphate

Shunt

Warburg Effect© 2010–2015 Cell Signaling Technology, Inc.

SGK

c-Raf

RasJnk

Gab

1

Shc

GRB2

GRB10

PI3Kp110

p85

IRS

IRS-1

SHIP

Cbl

Crk

ll

PTEN

SHP-2

MEK1/2

ROS

TSC2TSC1

eIF4E

Lipin1

Lipin1 4E-BP1

PRAS40GSK-3

PP1

Bad

ATP-citratelyase

p70S6K

Erk1/2

Erk1/2

Erk1/2Akt2

Akt

Akt2

PDK1

PDK1

PKCλ/ζ

PKCλ/ζ Fyn

SGK

PKA

SIK2

Torc2

AMPK

LKB1

Rheb

PKCθ

APS

PP2A

IKK

Insulin ReceptorTNF

AS160

TBC1D114-3-3

14-3-3

EHD1EHBP1

Rac1

PDE3B

SOCS3

TNFR

1

PTP1B

iNOS

HSL

Nck

ENaC

GS

C3GTC10

Cav

CA

P

Synip

CIP4/2

Flotillin

FoxO4 FoxO1USFLXRαSREBP

SREBP-1

SREBP

FoxO3

SOS

GLUT4

SNAREComplex

mTORC1

mTORC2

Crkll

CBP/p300

Apoptosis,Autophagy,Glucose andLipid Metabolism

Transcription

PIP3

GLUT4Translocation

GLUT4vesicle

Apoptosis

GlycogenSynthesis Fatty Acid

Synthesis

Fatty Acidand Cholesterol

SynthesisDisruption of

CBP/Torc2/CREBComplex

Gluconeogenesis

Growth

Protein Synthesis, Growth, and Proliferation

FFA

Glucose

Nucleus

SodiumTransport

NO

Lipolysis

Degradation

[cAMP]

GLUT4Exocytosis

Cytoplasm

mTORC2

mTORRictor

Sin1 PRR5

DEPTOR

RaptorGβLmTOR

DEPTOR

mTORC1

GβL

Insulin Receptor Signaling© 2003–2015 Cell Signaling Technology, Inc.