PTEN SHP-2 MEK1/2 ROS TSC2 TSC1 eIF4E 4E-BP1 PRAS40 GSK-3 PP1 Bad ATP-citrate lyase p70 S6K Erk1/2 Erk1/2 Erk1/2 Akt2

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Insulin Receptor Signaling Insulin Receptor TNF

GLUT4 Translocation

Crkll

C3G

TC10 CIP4/2

EHBP1

PDK1

TBC1D1 14-3-3

Bad

PRAS40

GSK-3

Apoptosis

SREBP-1 GS

PP1 ENaC

Akt2

ATP-citrate lyase

Glycogen Synthesis

LKB1

SGK

us

Nucle

FoxO3A

FoxO4 Transcription

Apoptosis mTORC1 GβL

Raptor mTOR

DEPTOR

FoxO1

TNFR1

Shc PDE3B

Rheb

[cAMP]

mTORC1

PKA

p70 S6K

IKK

NO

SOS GRB10

Jnk

Ras

iNOS c-Raf

SIK2 MEK1/2 CBP/p300

HSL Protein Synthesis

Akt2

Crkll

Fyn

ROS

AMPK

lasm

Cytop

FFA

eIF4E

Fatty Acid Synthesis

Sodium Transport

Nck

PKCθ

TSC2 TSC1

4E-BP1

PTP1B

IRS-1

mTORC2

14-3-3 AS160

SOCS3

GRB2

PDK1

PP2A

GLUT4 Exocytosis

SHP-2

PKCλ/ζ

PKCλ/ζ

GLUT4 vesicle

Akt2

EHD1

Rac1

SGK

SHIP

PIP3

IRS

Synip

p85 PI3K p110

PTEN

Cbl APS

CAP

FlotillinCav

Gab1

SNARE Complex

Glucose GLUT4

Torc2

Erk1/2

Degradation

Lipolysis Erk1/2

Fatty Acid Synthesis

Disruption of CBP/Torc2/CREB Complex SREBP-1

LXRα

USF

Gluconeogenesis

Erk1/2

mTORC2 Sin1

Growth

PRR5

Rictor mTOR

GβL DEPTOR

© 2006 – 2013 Cell Signaling Technology, Inc.

Insulin Receptor Signaling • created May 2006 • revised June 2012

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Signaling Pathways Key

Kinase Phosphatase Transcription Factor Caspase

Direct Stimulatory Modification Direct Inhibitory Modification Multistep Stimulatory Modification Multistep Inhibitory Modification Tentative Stimulatory Modification

Receptor

Tentative Inhibitory Modification

Enzyme

Transcriptional Stimulation

pro-apoptotic pro-survival

Transcriptional Inhibition Translocation Separation of Subunits or Cleavage Products

GAP / GEF GTPase G-protein Acetylase Deacetylase Ribosomal subunit

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Joining of Subunits