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Ligand. Receptor. Receptor/Ligand Binds to promoter elements in DNA and regulates transcription. Cortisol Receptor is located in the cytosol. Retinoid Receptors are in the nucleus. Nucleus:. Target gene in the nucleus. Promoter. Regulation of Transcription. Primary and Secondary Responses.

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Presentation Transcript
slide2

Ligand

Receptor

slide3

Receptor/Ligand Binds to promoter elements in DNA and regulates transcription

Cortisol Receptor is located in the cytosol

Retinoid Receptors are in the nucleus

Nucleus:

Target gene in the nucleus

Promoter

Regulation of Transcription

Primary and Secondary Responses

slide4

Promoter

Promoter

Activation of transcription

Inhibition of transcription

slide6

adenylyl

G protein

cyclase

receptor

extracellular

space

bg

a

membrane

cytosol

GDP

ligand

GTP

ATP

cAMP

Pi

slide8

Regulation of

Transcription

P

CREB

CRE

slide9

Some G protein linked receptors linked to Gq activate Ca2+ signaling

PIP2 plays an important role in Ca2+ signaling

PIP2

PI

slide10

PKC

ER

Ca2+

Calcium channel

Cleavage of PIP2 gives rise to Ca influx

Gq

(PLC b)

slide13

Regulation of

Transcription

P

CREB

CRE

cAMP phosphodiesterase and adenylyl cyclase

are regulated by CAM Kinases

PKA Ca channels

Some CAM Kinases are PKA targets

CAM Kinases and PKA common targets

Regulation of

Phosphorylase

Kinase by cAMP

and Ca

slide16

P

P

P

P

Ligand binding usually causes dimerization of the receptor

EGF

EGF

outside of the cell

Membrane

inside of the cell

slide17

GRB2

PLC

PI3K

GAP

P

P

P

P

Ras pathway

P-Tyr binds downstream regulators containing SH2 domains

SH2 Domain

slide18

GEF

G

D

P

G

T

P

G

A

P

Inactive

Active

Ras superfamily of small GTPases help relay signals from RTKs

Stimulus

Downstream

Signaling

Pathways

slide21

Drosophila Ras activation

GRB2

PLC

PI3K

GAP

P

P

P

P

Mammalian Ras activation

SH2 Domain

(DRK)

SOS

Ras

GTP

Downstream

pathways

slide22

MAP Kinase Pathways can be mediated by

members of the Ras superfamily

Stimulus

Usually Ras superfamily

slide25

GRB2

PLC

PI3K

GAP

P

P

P

P

Ca2+ signaling can be activated by RTKs via PLC g

Ca2+ signaling

slide26

ER

Ca2+

Calcium channel

Cleavage of PIP2 gives rise to Ca influx

RTK

PLCg

slide27

GRB2

PLC

PI3K

GAP

P

P

P

P

RTKs can activate PI3-Kinase

Other signaling pathways

Cell survival

slide28

C

C

C

C

H

H

H

H

2

2

2

2

C

C

C

C

H

H

H

H

2

2

2

2

C

C

C

C

C

C

C

C

O

O

O

O

O

O

O

O

O

O

O

O

O

O

O

O

C

C

C

C

H

H

H

H

C

C

C

C

H

H

H

H

2

2

2

2

C

C

C

C

H

H

H

H

2

2

2

2

O

O

O

O

O

O

O

O

P

P

P

P

O

O

O

O

-

-

-

-

O

O

O

O

H

H

H

H

O

O

O

O

6

6

6

6

5

5

5

5

4

4

4

4

1

1

1

1

3

3

3

3

2

2

2

2

O

O

O

O

H

H

H

H

O

O

O

O

H

H

H

H

PI3 Kinase (PI3K)

PI(3)P

PhosphatidylInositol(PI)

PI(3,4,5)P2

PI(3,4)P2

PI3K

PI3K

+

PI4K

+PI5K

Cell Survival Pathways

Other Signaling Pathways

slide29

C

C

C

C

H

H

H

H

2

2

2

2

C

C

C

C

H

H

H

H

2

2

2

2

C

C

C

C

C

C

C

C

O

O

O

O

O

O

O

O

O

O

O

O

O

O

O

O

C

C

C

C

H

H

H

H

C

C

C

C

H

H

H

H

2

2

2

2

C

C

C

C

H

H

H

H

2

2

2

2

O

O

O

O

O

O

O

O

P

P

P

P

O

O

O

O

-

-

-

-

O

O

O

O

H

H

H

H

O

O

O

O

6

6

6

6

5

5

5

5

4

4

4

4

1

1

1

1

3

3

3

3

2

2

2

2

P

H

O

O

O

O

H

H

H

H

O

O

O

O

H

H

H

H

P

H

P

S

E

R

A

K

T

P

D

K

1

ser

BAD

PI3 Kinase (PI3K) and cell survival pathways

PI(3)P

PhosphatidylInositol(PI)

PI(3,4,5)P2

PI(3,4)P2

PI3K

PI3K

+

PI4K

+PI5K

slide31

P

P

P

P

Tyrosine Kinase (TK) Associated Receptors

LIGAND

outside of the cell

Membrane

inside of the cell

slide33

GRB2

PLC

PI3K

P

P

P

P

Src

Cell proliferation,

Gene expression, …

slide34

LIGAND

P

P

receptors