cell signaling. pathways with friends helps understand…
TRANSCRIPT
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