Cell Signaling

Pathways with friends helps understand…

Learning Targets

1. I can summarize what is occurring in the three stages of cell communication: reception, transduction and response.

2. I can describe how the following receive cell signals and start transduction: G-protein coupled receptors tyrosine kinase receptors ion channels

3. I can identify and describe the role of second messengers such as cyclic AMP and Ca2+

4. I can describe how a cell signal is amplified by a phosphorylation cascade.

5. I can describe how a cellular response in the nucleus differs from a cellular response in the cytoplasm.

6. I can explain what apoptosis means and why it is important for normal functioning of multicellular organisms.

Focus Questions1. Why do cells need to communicate?

2. Explain what happens during the three phases of signal transduction.

3. What is the purpose of second messengers?

4. Diagram the epinephrine signaling pathway. Diagram signal reception, transduction and response.

5. Define each of the following phenomena, identify the organisms that they occur in, and explain how cellular signaling is used in each of them:a. Quorum Sensingb. Apoptosis

6. Why do you think cellular signaling pathways and mechanisms are so universal among life’s domains?

7. What are the similarities and differences in G-Protein, Tyrosine Kinase, and ligant-gated ion channel signaling pathways?

8. How does a signaling pathway lead to an amplification of the response to the signal?

9. How can a signaling pathway have multiple physiological effects on a cell or organism?

Figure 11.5a

Local signaling

Target cell

Secretingcell

Secretoryvesicle

Local regulatordiffuses throughextracellular fluid.

(a) Paracrine signaling (b) Synaptic signaling

Electrical signalalong nerve celltriggers release ofneurotransmitter.

Neurotransmitter diffuses across synapse.

Target cellis stimulated.

Different Ligands have different receptors

Figure 11.6-1

Plasma membrane

EXTRACELLULARFLUID

CYTOPLASM

Reception

Receptor

Signalingmolecule

1

Figure 11.6-2

Plasma membrane

EXTRACELLULARFLUID

CYTOPLASM

Reception Transduction

Receptor

Signalingmolecule

Relay molecules in a signal transductionpathway

21

Figure 11.6-3

Plasma membrane

EXTRACELLULARFLUID

CYTOPLASM

Reception Transduction Response

Receptor

Signalingmolecule

Activationof cellularresponse

Relay molecules in a signal transductionpathway

321

Figure 11.7b

G protein-coupledreceptor

21

3 4

Plasmamembrane

G protein(inactive)

CYTOPLASM Enzyme

Activatedreceptor

Signalingmolecule

Inactiveenzyme

Activatedenzyme

Cellular response

GDPGTP

GDPGTP

GTP

P i

GDP

GDP

Figure 11.7c

Signalingmolecule (ligand)

21

3 4

Ligand-binding site

helix in themembrane

Tyrosines

CYTOPLASM Receptor tyrosinekinase proteins(inactive monomers)

Signalingmolecule

Dimer

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

Tyr

P

P

P

P

P

P

P

P

P

P

P

P

Activated tyrosinekinase regions(unphosphorylateddimer)

Fully activatedreceptor tyrosinekinase(phosphorylateddimer)

Activated relayproteins

Cellularresponse 1

Cellularresponse 2

Inactiverelay proteins

6 ATP 6 ADP

Figure 11.7d

Signalingmolecule (ligand)

21 3

Gate closed Ions

Ligand-gatedion channel receptor

Plasmamembrane

Gate open

Cellularresponse

Gate closed

Figure 11.9-1

Hormone(testosterone)

Receptorprotein

Plasmamembrane

DNA

NUCLEUS

CYTOPLASM

EXTRACELLULARFLUID

Figure 11.9-2

Hormone(testosterone)

Receptorprotein

Plasmamembrane

Hormone-receptorcomplex

DNA

NUCLEUS

CYTOPLASM

EXTRACELLULARFLUID

Figure 11.9-3

Hormone(testosterone)

Receptorprotein

Plasmamembrane

Hormone-receptorcomplex

DNA

NUCLEUS

CYTOPLASM

EXTRACELLULARFLUID

Figure 11.9-4

Hormone(testosterone)

Receptorprotein

Plasmamembrane

Hormone-receptorcomplex

DNA

mRNA

NUCLEUS

CYTOPLASM

EXTRACELLULARFLUID

Figure 11.9-5

Hormone(testosterone)

Receptorprotein

Plasmamembrane

EXTRACELLULARFLUID

Hormone-receptorcomplex

DNA

mRNA

NUCLEUS

CYTOPLASM

New protein

Figure 11.10

Receptor

Signaling molecule

Activated relaymolecule

Phosphorylation cascade

Inactiveprotein kinase

1 Activeprotein kinase

1

Activeprotein kinase

2

Activeprotein kinase

3

Inactiveprotein kinase

2

Inactiveprotein kinase

3

Inactiveprotein

Activeprotein

Cellularresponse

ATPADP

ATPADP

ATPADP

PP

PP

PP

P

P

P

P i

P i

P i

Figure 11.16

Reception

Transduction

Response

Binding of epinephrine to G protein-coupled receptor (1 molecule)

Inactive G protein

Active G protein (102 molecules)

Inactive adenylyl cyclaseActive adenylyl cyclase (102)

ATPCyclic AMP (104)

Inactive protein kinase AActive protein kinase A (104)

Inactive phosphorylase kinase

Active phosphorylase kinase (105)

Inactive glycogen phosphorylase

Active glycogen phosphorylase (106)

Glycogen

Glucose 1-phosphate (108 molecules)

Figure 11.15

Growth factor

Receptor

Reception

Transduction

CYTOPLASM

Response

Inactivetranscriptionfactor

Activetranscriptionfactor

DNA

NUCLEUS mRNA

Gene

Phosphorylationcascade

P

Figure 11.17

Wild type (with shmoos) Fus3 formin

Matingfactoractivatesreceptor.

Matingfactor G protein-coupled

receptor

Shmoo projectionforming

Formin

G protein binds GTPand becomes activated.

2

1

3

4

5

P

P

P

PForminFormin

Fus3

Fus3Fus3

GDPGTP

Phosphory- lation cascade

Microfilament

Actinsubunit

Phosphorylation cascadeactivates Fus3, which movesto plasma membrane.

Fus3 phos-phorylatesformin,activating it.

Formin initiates growth ofmicrofilaments that formthe shmoo projections.

RESULTS

CONCLUSION

Figure 11.18

Signalingmolecule

Receptor

Relay molecules

Response 1

Cell A. Pathway leadsto a single response.

Response 2 Response 3 Response 4 Response 5

Activationor inhibition

Cell B. Pathway branches,leading to two responses.

Cell C. Cross-talk occursbetween two pathways.

Cell D. Different receptorleads to a differentresponse.

Why does epinephrine have 2 very different responses?

Figure 11.21

Mitochondrion

Ced-9protein (active)inhibits Ced-4activity

Receptorfor death-signalingmolecule

Ced-4 Ced-3

Inactive proteins

(a) No death signal

Death-signalingmolecule

Ced-9(inactive)

Cellformsblebs

ActiveCed-4

ActiveCed-3

Otherproteases

NucleasesActivationcascade

(b) Death signal

APOPTOSIS

Figure 11.22

Interdigital tissueCells undergoing

apoptosisSpace between

digits1 mm

DRAW IT

A DEATH SIGNAL IS RECEIVED WHEN A MOLECULE CALLED FAS BINDS ITS CELL-SURFACE RECEPTOR.

THE BINDING OF MANY FAS MOLECULES TO RECEPTORS CAUSES RECEPTOR CLUSTERING.

THE INTRACELLULAR REGIONS OF THE RECEPTORS, WHEN TOGETHER BIND PROTEINS CALLED ADAPTOR PROTEINS.

THESE, IN TURN, BIND TO INACTIVE MOLECULES OF CAPASE-8, WHICH BECOME ACTIVATED

ACTIVE CAPASE-8 THEN ACTIVATED CAPASE-3.

ACTIVE CAPASE-3 INITIATES APOPTOSIS

Figure 11.UN02

2012 Nobel Prize Awarded for work on G Coupled Protein Receptors

Robert Lefkowitz Brian Kobilka