CST Signaling PaThway DiagramS for

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Cell Biology

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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

cdc42

Par6 aPKCPar3

Rac1

Rac1

TauRho

Rho

mDIA

mDIA1

Erk

DvlTAOK

MARKMARK2TESK

Spred1

Cofilin

LIMK

TPPP LL5β

Par1

Akt PTEN ROCK

PI3K

Wnt

LRP

APC

APC

mDIA EB1CLASP

CLASP

EB1

EB1

CLIPCLIP

Stat3

ICIS

MAP1b

XMAP215MCAK

MAP1bCRMP2

MAPKAPK

GSK-3β

PKA

CaMKCdk1

Aurora B

PAKErk

Stathmin

CLIP

CLIP

c-Abl

Trio

Tiam1

Src

Rho

RhoRhoGEF

RTKNeurotrophins

Gα

Gαq/o

Delivery toMT Plus Ends

MT Stability

Plus EndProteins

Actin Filaments

MTPolymerization

MTPolymerization

Plus End Minus End

+ end GrowthPromoting +/- end

Destabilizing

MT Catastrophe

Dynamic MTs

Focal Adhesions

PIP3

PIP3

Regulation of Microtubule Dynamics© 2008–2015 Cell Signaling Technology, Inc.

Ub

Ub

Ub

UbUb

UbUb

Ub

UbUb

Ub

Ub

UbUb

UbUb

UbUbUb

UbUb

Ub

UbUb

UbUb

UbUb

UbUb

UbUb

UbUb

UbUb

UbUb

UbUb

UbUb

UbUb

UbUb

E1E1

E2 E1

E2

E2

E3

DUBs

DUBs

E3 Mono-Ub

ATP AMP

26SProteasome

Peptides

ADPATP

ProteinSubstrate

EndocytosisDNA Repair

Protein LocalizationTrafficking

MultipleCycles

Multi-Mono-Ub

K48 Poly-Ub K11 Poly-Ub K6 Poly-Ub K27 Poly-Ub K29 Poly-Ub K33 Poly-Ub K63 Poly-Ub Linear Poly-Ub

DNA DamageResponse

MitochondrialMaintenance and Mitophagy

LysomalDegradation

TCR Signaling

Activating NF-κBSignaling

19S

20S

19S

Ubiquitin/Proteasome© 2004–2015 Cell Signaling Technology, Inc.

SrcFAK

Grb2

GRB2

p130

Cofilin

14-3-3ζ

Mical

GIT1/2

Nck

WASP

Ras

RacCrk

Cortactin

Tropomyosins

WAVEPI5K

PAK1

MEKK

PI3K

PKD1

PI3K

MEKK

MEKPAK1

MBS

Rho

mDIAROCKROCK

LIMK MLCK

MLCK

MLCCalcineurin

Arp2/3

Arp2/3

SSH

CaM

CIN Cofilin

Hsp90

ADF

CapZ

Tmod

mDIA

Filamin

FilaminProfilin

Gelsolin

PIX

PIXTIAM1

Vav

cdc42

CaM

VASP

WASP

Ena

Fascin

GEF

PAK1

PLCγ

PKCαPLCβ

PKA

RhoGEF

PI3KPI3K

PI3Kα

Paxillin

RTK

PlexinA

Severed Filaments

Sema1aIntegrin

Receptor

Ca2+

Ca2+

PIP3

PIP2

PIP3

PIP3

PIP2

LamellipodiaActin

Polymerization

FilopodiaBarbed-end

Cappers

Pointed-endCappers

Filopodia

NADPH

F-actinBundles/Meshworks

NADP

Degradation

Stress Fibers

Lamellipodia

IP3

G13

GPCR

Gi Gq Gs

Regulation of Actin Dynamics© 2008–2015 Cell Signaling Technology, Inc.

Formation

Maintenance

Disassembly

Caveolin

Clathrin

β-cat

β-cat

β-cat

β-cat

β-cat

AfadinSH2D1A

c-Cbl

Ajuba

Arp2/3

RaIA

Src

SrcPTP1B

Rac

Akt

PRK1

PI3K

WASP

cdc42

Rac

RacFyn

Cytoplasm

AdherensJunctionRemodeling

Cytoplasm

Cytoplasm

ExtracellularSpace

Nucleus

Nectin

Nectin

CadherinCadherin

PTPµ

ROCK

Kaiso

LEF/TCF

Cortactin

ARHGAP1

Arp2/3

CK2

VE-Cadherin

Occludin

IQGAP

IQGAP

IRSp53

Rap1

GSK-3

APC

MLC

Gβ1

Tiam1

Ect2

Par3/6WASP

Cip4

aPKC

LAMTOR1

APC

Formin

Vinculin

IQGAP

Afadin

Axin1

β-cat

β-cat

β-cat

α-cat

α-cat

α-cat

α-cat

γ-cat

δ-catδ-cat

δ-cat

δ-cat

δ-cat

α-cat

UbUbUbE3

Ub

UbUb

Ub

α

α α-actinin

Actin bundles

αmDIA

p190RhoA

RhoA

Cadh

erin

End

ocyt

osis

β-cat

Vinculin

δ-cat

α-catβ-cat

• Actin Nucleation• Actin Dynamics

• Anti-Apoptotic Signals• Apoptosis• Angiogenesis

IncreasedActomycinContractility

CadherinDegradation

CadherinRecycling

ActinDisassembly

Cell Growth & DifferentiationCaveolin/Clathrin

Phagosome

CentralspindlinComplex

β-cateninDegradation

WntSignaling

Adherens Junction Dynamics© 2008–2015 Cell Signaling Technology, Inc.