6
Time (min) Time (min) 0 1 3 5 10152030 50 ng/ml NGF P-p38 T-p38 5 ng/ml NGF 300 100 50 30 10 5 1 0 NGF (ng/ml) 0 10 20 30 50 ng/ml NGF 5 ng/ml NGF 8 Log [NGF] (ng/ml) p38 MAPK phosphorylation (Fold stimulation) p38 MAPK phosphorylation (Fold stimulation) 0 2 4 6 8 1001000 1 10 2 6 4 P-p38 T-p38 P-p38 T-p38 B C NGF Control NGF + SB203580 NGF + SB202190 A Figure 1

Time (min)

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Figure 1. 50 ng/ml NGF. 5 ng/ml NGF. A. NGF + SB203580. Control. NGF + SB202190. NGF. B. 8. 6. p38 MAPK phosphorylation (Fold stimulation). 4. 2. 0. 10. 20. 30. Time (min). P-p38 T-p38. 5 ng/ml NGF. P-p38 T-p38. 50 ng/ml NGF. Time (min). 0. 1. 3. 5. 10. 15. - PowerPoint PPT Presentation

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Page 1: Time (min)

Time (min)

Time (min) 0 1 3 5 10 15 20 30

50 ng/ml NGF

P-p38T-p38

5 ng/mlNGF

300

100

503010510

NGF (ng/ml)

0 10 20 30

50 ng/ml NGF 5 ng/ml NGF

8

Log [NGF] (ng/ml)

p38

MA

PK

ph

osp

hor

ylat

ion

(Fol

d s

tim

ula

tion

)

p38

MA

PK

p

hos

ph

oryl

atio

n(F

old

sti

mu

lati

on)

0

2

4

6

8

100 10001 10

2

6

4

P-p38T-p38

P-p38T-p38

B

C

NGF

ControlNGF +

SB203580

NGF +SB202190

AFigure 1

Page 2: Time (min)

C

0

2

4

6Basal 5 ng/ml NGF

PTX

PTX

2

4

6

0

#

**

p38

MA

PK

ph

osp

hor

ylat

ion

(

Fol

d s

tim

ula

tion

)

# #

*

** **

* *

Con

trol

G z

G oA

CI

G i2

/z

G oA

G i2

P-p38T-p38

P-p38T-p38

p38

MA

PK

ph

osp

hor

ylat

ion

(Fol

d s

tim

ula

tion

)

6

4

2

0

PTX

Control 5 ng/ml NGF

50 ng/ml NGF

#

8

* *#

A

P-p38T-p38

Figure 2

PTX

NGF

P-p38T-p38

B

Page 3: Time (min)

Gi2GTGi2

PTX

2

4

6

0P-p38T-p38

#

2

4

6

0

*

P-p38T-p38

PTXB

p38

MA

PK

ph

osp

hor

ylat

ion

(

Fol

d s

tim

ula

tion

)

A

IgG

Trk

A

IgG

Trk

A

NGF NGF

P-TrkA

Gi2

Gz

Go

WB

IP IP

Lys

ate

Lys

ate

Figure 3

Page 4: Time (min)

A

0

2

4

6

*

p38

MA

PK

ph

osp

hor

ylat

ion

(F

old

sti

mu

lati

on)

*

#

*

U01

26

Con

trol

NG

F

P-p38T-p38

U01

24

SP

6001

25

BBasal 5 ng/ml NGF 5 ng/ml NGF + inhibitor

MA

PK

ph

osp

hor

ylat

ion

(F

old

sti

mu

lati

on)

*

#048

10*

#

1214

*

P-MAPK

T-MAPK

U01

24U

0126

Con

trol

NG

F

SP

6001

25

Con

trol

NG

F

JNKERK

Figure 4

Page 5: Time (min)

0

2

4

6

Con

trol

NG

FA

G49

0

SU

6656

PP

1

p38

MA

PK

p

hos

ph

oryl

atio

n

(Fol

d s

tim

ula

tion

)

PP

2P

P3

**

# #

#

**

AG

1295

ABasal 5 ng/ml NGF 5 ng/ml NGF + inhibitor

B

P-p38T-p38

W7

Con

trol

NG

FK

N62

Sta

uro

spor

ine

U73

122

Cal

ph

osti

n C

U73

343

* **

**

* *

Src

ph

osp

hor

ylat

ion

(Fol

d s

tim

ula

tion

)

0

PTX

P-Src

T-Src

1

2 *3

#

C

Figure 5

Page 6: Time (min)

C3GC3G

Rap1Rap1

RhoARhoA

RhoGEF

RhoGEF

GG

B-RafB-Raf

NGF

Trk A receptor

CrkCrk

GIPC1GIPC1GAIP

GAIP

p38 MAPK

Rac/cdc42

Rac/cdc42

MKK3/6MKK3/6

MLKsMLKs

MKK4MKK4

MEKK1-4MEKK1-4

RasRas

Gi2

Gi2

MEK1/2

Gi2 Src

Src

Figure 6