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Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
PowerPoint Lectures for
Biology, Seventh Edition
Neil Campbell and Jane Reece
Lectures by Chris Romero
Chapter 11
Cell Communication
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Overview: The Cellular Internet
• Cell-to-cell communication
– Is absolutely essential for multicellular
organisms
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Biologists
– Have discovered some universal mechanisms
of cellular regulation
Figure 11.1
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Concept 11.1: External signals are converted
into responses within the cell
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Evolution of Cell Signaling
• Yeast cells
– Identify their mates by cell signaling
 factor
Receptor
Exchange of
mating factors.
Each cell type
secretes a
mating factor
that binds to
receptors on
the other cell
type.
1
Mating. Binding
of the factors to
receptors
induces changes
in the cells that
lead to their
fusion.
New a/ cell.
The nucleus of
the fused cell
includes all the
genes from the
a and a cells.
2
3
 factor
Yeast cell,
mating type a
Yeast cell,
mating type 


a/
a
a
Figure 11.2
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Signal transduction pathways
– Convert signals on a cell’s surface into cellular
responses
– Are similar in microbes and mammals,
suggesting an early origin
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Local and Long-Distance Signaling
• Cells in a multicellular organism
– Communicate via chemical messengers
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Animal and plant cells
– Have cell junctions that directly connect the
cytoplasm of adjacent cells
Plasma membranes
Plasmodesmata
between plant cells
Gap junctions
between animal cells
Figure 11.3 (a) Cell junctions. Both animals and plants have cell junctions that allow molecules
to pass readily between adjacent cells without crossing plasma membranes.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Figure 11.3 (b) Cell-cell recognition. Two cells in an animal may communicate by interaction
between molecules protruding from their surfaces.
• In local signaling, animal cells
– May communicate via direct contact
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• In other cases, animal cells
– Communicate using local regulators
(a) Paracrine signaling. A secreting cell acts
on nearby target cells by discharging
molecules of a local regulator (a growth
factor, for example) into the extracellular
fluid.
(b) Synaptic signaling. A nerve cell
releases neurotransmitter molecules
into a synapse, stimulating the
target cell.
Local regulator
diffuses through
extracellular fluid
Target cell
Secretory
vesicle
Electrical signal
along nerve cell
triggers release of
neurotransmitter
Neurotransmitter
diffuses across
synapse
Target cell
is stimulated
Local signaling
Figure 11.4 A B
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• In long-distance signaling
– Both plants and animals use hormones
Hormone travels
in bloodstream
to target cells
(c) Hormonal signaling. Specialized
endocrine cells secrete hormones
into body fluids, often the blood.
Hormones may reach virtually all
body cells.
Long-distance signaling
Blood
vessel
Target
cell
Endocrine cell
Figure 11.4 C
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
The Three Stages of Cell Signaling: A Preview
• Earl W. Sutherland
– Discovered how the hormone epinephrine acts
on cells
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Sutherland suggested that cells receiving
signals went through three processes
– Reception
– Transduction
– Response
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
EXTRACELLULAR
FLUID
Receptor
Signal
molecule
Relay molecules in a signal transduction pathway
Plasma membrane
CYTOPLASM
Activation
of cellular
response
Figure 11.5
• Overview of cell signaling
Reception
1 Transduction
2 Response
3
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Concept 11.2: Reception: A signal molecule
binds to a receptor protein, causing it to
change shape
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• The binding between signal molecule (ligand)
– And receptor is highly specific
• A conformational change in a receptor
– Is often the initial transduction of the signal
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Intracellular Receptors
• Intracellular receptors
– Are cytoplasmic or nuclear proteins
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Signal molecules that are small or hydrophobic
– And can readily cross the plasma membrane
use these receptors
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Receptor
protein
DNA
mRNA
NUCLEUS
CYTOPLASM
Plasma
membrane
Hormone-
receptor
complex
New protein
Figure 11.6
• Steroid hormones
– Bind to intracellular receptors
1 The steroid
hormone testosterone
passes through the
plasma membrane.
The bound protein
stimulates the
transcription of
the gene into mRNA.
4
The mRNA is
translated into a
specific protein.
5
Testosterone binds
to a receptor protein
in the cytoplasm,
activating it.
2
The hormone-
receptor complex
enters the nucleus
and binds to specific
genes.
3
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Receptors in the Plasma Membrane
• There are three main types of membrane
receptors
– G-protein-linked
– Tyrosine kinases
– Ion channel
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• G-protein-linked receptors
G-protein-linked
Receptor
Plasma Membrane
Enzyme
G-protein
(inactive)
CYTOPLASM
Cellular response
Activated
enzyme
Activated
Receptor
Signal molecule
Inctivate
enzyme
Segment that
interacts with
G proteins
GDP
GDP
GTP
GTP
P i
Signal-binding site
Figure 11.7
GDP
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Receptor tyrosine kinases
Signal
molecule
Signal-binding sitea
CYTOPLASM
Tyrosines
Signal
molecule
Helix in the
Membrane
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
Dimer
Receptor tyrosine
kinase proteins
(inactive monomers)
P
P
P
P
P
P Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
P
P
P
P
P
P
Cellular
response 1
Inactive
relay proteins
Activated
relay proteins
Cellular
response 2
Activated tyrosine-
kinase regions
(unphosphorylated
dimer)
Fully activated receptor
tyrosine-kinase
(phosphorylated
dimer)
6 ATP 6 ADP
Figure 11.7
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Ion channel receptors
Cellular
response
Gate open
Gate close
Ligand-gated
ion channel receptor
Plasma
Membrane
Signal
molecule
(ligand)
Figure 11.7
Gate
closed Ions
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Concept 11.3: Transduction: Cascades of
molecular interactions relay signals from
receptors to target molecules in the cell
• Multistep pathways
– Can amplify a signal
– Provide more opportunities for coordination
and regulation
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Signal Transduction Pathways
• At each step in a pathway
– The signal is transduced into a different form,
commonly a conformational change in a
protein
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Protein Phosphorylation and Dephosphorylation
• Many signal pathways
– Include phosphorylation cascades
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• In this process
– A series of protein kinases add a phosphate to
the next one in line, activating it
– Phosphatase enzymes then remove the
phosphates
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Signal molecule
Active
protein
kinase
1
Active
protein
kinase
2
Active
protein
kinase
3
Inactive
protein kinase
1
Inactive
protein kinase
2
Inactive
protein kinase
3
Inactive
protein
Active
protein
Cellular
response
Receptor
P
P
P
ATP
ADP
ADP
ADP
ATP
ATP
PP
PP
PP
Activated relay
molecule
i
P
P
i
i
P
• A phosphorylation cascade
Figure 11.8
A relay molecule
activates protein kinase 1.
1
2 Active protein kinase 1
transfers a phosphate from ATP
to an inactive molecule of
protein kinase 2, thus activating
this second kinase.
Active protein kinase 2
then catalyzes the phos-
phorylation (and activation) of
protein kinase 3.
3
Finally, active protein
kinase 3 phosphorylates a
protein (pink) that brings
about the cell’s response to
the signal.
4
Enzymes called protein
phosphatases (PP)
catalyze the removal of
the phosphate groups
from the proteins,
making them inactive
and available for reuse.
5
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Small Molecules and Ions as Second Messengers
• Second messengers
– Are small, nonprotein, water-soluble molecules
or ions
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Cyclic AMP
• Cyclic AMP (cAMP)
– Is made from ATP
Figure 11.9
O
–
O O
O
N
O
O
O
O
P P P
P
P P
O
O
O
O
O
OH
CH2
NH2 NH2 NH2
N
N
N
N
N
N
N
N
N
N
N
O
O
O
ATP
Ch2 CH2
O
OH OH
P
O O
H2O
HO
Adenylyl cyclase Phoshodiesterase
Pyrophosphate
Cyclic AMP AMP
OH OH
O
i
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Many G-proteins
– Trigger the formation of cAMP, which then acts
as a second messenger in cellular pathways
ATP
GTP
cAMP
Protein
kinase A
Cellular responses
G-protein-linked
receptor
Adenylyl
cyclase
G protein
First messenger
(signal molecule
such as epinephrine)
Figure 11.10
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Calcium ions and Inositol Triphosphate (IP3)
• Calcium, when released into the cytosol of a
cell
– Acts as a second messenger in many different
pathways
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Calcium is an important second messenger
– Because cells are able to regulate its
concentration in the cytosol
EXTRACELLULAR
FLUID
Plasma
membrane
ATP
CYTOSOL
ATP Ca2+
pump
Ca2+
pump
Ca2+
pump
Endoplasmic
reticulum (ER)
Nucleus
Mitochondrion
Key High [Ca2+] Low [Ca2+]
Figure 11.11
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Other second messengers such as inositol
triphosphate and diacylglycerol
– Can trigger an increase in calcium in the cytosol
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Figure 11.12
3
2
1
IP3 quickly diffuses through
the cytosol and binds to an IP3–
gated calcium channel in the ER
membrane, causing it to open.
4 The calcium ions
activate the next
protein in one or more
signaling pathways.
6
Calcium ions flow out of
the ER (down their con-
centration gradient), raising
the Ca2+ level in the cytosol.
5
DAG functions as
a second messenger
in other pathways.
Phospholipase C cleaves a
plasma membrane phospholipid
called PIP2 into DAG and IP3.
A signal molecule binds
to a receptor, leading to
activation of phospholipase C.
EXTRA-
CELLULAR
FLUID
Signal molecule
(first messenger)
G protein
G-protein-linked
receptor
Various
proteins
activated
Endoplasmic
reticulum (ER)
Phospholipase C
PIP2
IP3
(second messenger)
DAG
Cellular
response
GTP
Ca2+
(second
messenger)
Ca2+
IP3-gated
calcium channel
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Concept 11.4: Response: Cell signaling leads
to regulation of cytoplasmic activities or
transcription
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Cytoplasmic and Nuclear Responses
• In the cytoplasm
– Signaling pathways regulate a variety of
cellular activities
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Cytoplasmic response to a signal
Figure 11.13
Glucose-1-phosphate
(108 molecules)
Glycogen
Active glycogen phosphorylase (106)
Inactive glycogen phosphorylase
Active phosphorylase kinase (105)
Inactive phosphorylase kinase
Inactive protein kinase A
Active protein kinase A (104)
ATP
Cyclic AMP (104)
Active adenylyl cyclase (102)
Inactive adenylyl cyclase
Inactive G protein
Active G protein (102 molecules)
Binding of epinephrine to G-protein-linked receptor (1 molecule)
Transduction
Response
Reception
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Other pathways
– Regulate genes by activating transcription
factors that turn genes on or off
Reception
Transduction
Response
mRNA
NUCLEUS
Gene
P
Active
transcription
factor
Inactive
transcription
factor
DNA
Phosphorylation
cascade
CYTOPLASM
Receptor
Growth factor
Figure 11.14
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Fine-Tuning of the Response
• Signal pathways with multiple steps
– Can amplify the signal and contribute to the
specificity of the response
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Signal Amplification
• Each protein in a signaling pathway
– Amplifies the signal by activating multiple
copies of the next component in the pathway
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
The Specificity of Cell Signaling
• The different combinations of proteins in a cell
– Give the cell great specificity in both the
signals it detects and the responses it carries
out
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Pathway branching and “cross-talk”
– Further help the cell coordinate incoming
signals
Response 1
Response 4 Response 5
Response
2
Response
3
Signal
molecule
Cell A. Pathway leads
to a single response
Cell B. Pathway branches,
leading to two responses
Cell C. Cross-talk occurs
between two pathways
Cell D. Different receptor
leads to a different response
Activation
or inhibition
Receptor
Relay
molecules
Figure 11.15
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Signaling Efficiency: Scaffolding Proteins and
Signaling Complexes
• Scaffolding proteins
– Can increase the signal transduction efficiency
Signal
molecule
Receptor
Scaffolding
protein
Three
different
protein
kinases
Plasma
membrane
Figure 11.16
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Termination of the Signal
• Signal response is terminated quickly
– By the reversal of ligand binding

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Cell Communication Mechanisms and Pathways

  • 1. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings PowerPoint Lectures for Biology, Seventh Edition Neil Campbell and Jane Reece Lectures by Chris Romero Chapter 11 Cell Communication
  • 2. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Overview: The Cellular Internet • Cell-to-cell communication – Is absolutely essential for multicellular organisms
  • 3. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Biologists – Have discovered some universal mechanisms of cellular regulation Figure 11.1
  • 4. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Concept 11.1: External signals are converted into responses within the cell
  • 5. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Evolution of Cell Signaling • Yeast cells – Identify their mates by cell signaling  factor Receptor Exchange of mating factors. Each cell type secretes a mating factor that binds to receptors on the other cell type. 1 Mating. Binding of the factors to receptors induces changes in the cells that lead to their fusion. New a/ cell. The nucleus of the fused cell includes all the genes from the a and a cells. 2 3  factor Yeast cell, mating type a Yeast cell, mating type    a/ a a Figure 11.2
  • 6. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Signal transduction pathways – Convert signals on a cell’s surface into cellular responses – Are similar in microbes and mammals, suggesting an early origin
  • 7. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Local and Long-Distance Signaling • Cells in a multicellular organism – Communicate via chemical messengers
  • 8. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Animal and plant cells – Have cell junctions that directly connect the cytoplasm of adjacent cells Plasma membranes Plasmodesmata between plant cells Gap junctions between animal cells Figure 11.3 (a) Cell junctions. Both animals and plants have cell junctions that allow molecules to pass readily between adjacent cells without crossing plasma membranes.
  • 9. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 11.3 (b) Cell-cell recognition. Two cells in an animal may communicate by interaction between molecules protruding from their surfaces. • In local signaling, animal cells – May communicate via direct contact
  • 10. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • In other cases, animal cells – Communicate using local regulators (a) Paracrine signaling. A secreting cell acts on nearby target cells by discharging molecules of a local regulator (a growth factor, for example) into the extracellular fluid. (b) Synaptic signaling. A nerve cell releases neurotransmitter molecules into a synapse, stimulating the target cell. Local regulator diffuses through extracellular fluid Target cell Secretory vesicle Electrical signal along nerve cell triggers release of neurotransmitter Neurotransmitter diffuses across synapse Target cell is stimulated Local signaling Figure 11.4 A B
  • 11. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • In long-distance signaling – Both plants and animals use hormones Hormone travels in bloodstream to target cells (c) Hormonal signaling. Specialized endocrine cells secrete hormones into body fluids, often the blood. Hormones may reach virtually all body cells. Long-distance signaling Blood vessel Target cell Endocrine cell Figure 11.4 C
  • 12. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The Three Stages of Cell Signaling: A Preview • Earl W. Sutherland – Discovered how the hormone epinephrine acts on cells
  • 13. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Sutherland suggested that cells receiving signals went through three processes – Reception – Transduction – Response
  • 14. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings EXTRACELLULAR FLUID Receptor Signal molecule Relay molecules in a signal transduction pathway Plasma membrane CYTOPLASM Activation of cellular response Figure 11.5 • Overview of cell signaling Reception 1 Transduction 2 Response 3
  • 15. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Concept 11.2: Reception: A signal molecule binds to a receptor protein, causing it to change shape
  • 16. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • The binding between signal molecule (ligand) – And receptor is highly specific • A conformational change in a receptor – Is often the initial transduction of the signal
  • 17. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Intracellular Receptors • Intracellular receptors – Are cytoplasmic or nuclear proteins
  • 18. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Signal molecules that are small or hydrophobic – And can readily cross the plasma membrane use these receptors
  • 19. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Hormone (testosterone) EXTRACELLULAR FLUID Receptor protein DNA mRNA NUCLEUS CYTOPLASM Plasma membrane Hormone- receptor complex New protein Figure 11.6 • Steroid hormones – Bind to intracellular receptors 1 The steroid hormone testosterone passes through the plasma membrane. The bound protein stimulates the transcription of the gene into mRNA. 4 The mRNA is translated into a specific protein. 5 Testosterone binds to a receptor protein in the cytoplasm, activating it. 2 The hormone- receptor complex enters the nucleus and binds to specific genes. 3
  • 20. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Receptors in the Plasma Membrane • There are three main types of membrane receptors – G-protein-linked – Tyrosine kinases – Ion channel
  • 21. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • G-protein-linked receptors G-protein-linked Receptor Plasma Membrane Enzyme G-protein (inactive) CYTOPLASM Cellular response Activated enzyme Activated Receptor Signal molecule Inctivate enzyme Segment that interacts with G proteins GDP GDP GTP GTP P i Signal-binding site Figure 11.7 GDP
  • 22. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Receptor tyrosine kinases Signal molecule Signal-binding sitea CYTOPLASM Tyrosines Signal molecule Helix in the Membrane 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 Dimer Receptor tyrosine kinase proteins (inactive monomers) P P P P P P Tyr Tyr Tyr Tyr Tyr Tyr P P P P P P Cellular response 1 Inactive relay proteins Activated relay proteins Cellular response 2 Activated tyrosine- kinase regions (unphosphorylated dimer) Fully activated receptor tyrosine-kinase (phosphorylated dimer) 6 ATP 6 ADP Figure 11.7
  • 23. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Ion channel receptors Cellular response Gate open Gate close Ligand-gated ion channel receptor Plasma Membrane Signal molecule (ligand) Figure 11.7 Gate closed Ions
  • 24. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Concept 11.3: Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell • Multistep pathways – Can amplify a signal – Provide more opportunities for coordination and regulation
  • 25. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Signal Transduction Pathways • At each step in a pathway – The signal is transduced into a different form, commonly a conformational change in a protein
  • 26. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Protein Phosphorylation and Dephosphorylation • Many signal pathways – Include phosphorylation cascades
  • 27. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • In this process – A series of protein kinases add a phosphate to the next one in line, activating it – Phosphatase enzymes then remove the phosphates
  • 28. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Signal molecule Active protein kinase 1 Active protein kinase 2 Active protein kinase 3 Inactive protein kinase 1 Inactive protein kinase 2 Inactive protein kinase 3 Inactive protein Active protein Cellular response Receptor P P P ATP ADP ADP ADP ATP ATP PP PP PP Activated relay molecule i P P i i P • A phosphorylation cascade Figure 11.8 A relay molecule activates protein kinase 1. 1 2 Active protein kinase 1 transfers a phosphate from ATP to an inactive molecule of protein kinase 2, thus activating this second kinase. Active protein kinase 2 then catalyzes the phos- phorylation (and activation) of protein kinase 3. 3 Finally, active protein kinase 3 phosphorylates a protein (pink) that brings about the cell’s response to the signal. 4 Enzymes called protein phosphatases (PP) catalyze the removal of the phosphate groups from the proteins, making them inactive and available for reuse. 5
  • 29. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Small Molecules and Ions as Second Messengers • Second messengers – Are small, nonprotein, water-soluble molecules or ions
  • 30. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cyclic AMP • Cyclic AMP (cAMP) – Is made from ATP Figure 11.9 O – O O O N O O O O P P P P P P O O O O O OH CH2 NH2 NH2 NH2 N N N N N N N N N N N O O O ATP Ch2 CH2 O OH OH P O O H2O HO Adenylyl cyclase Phoshodiesterase Pyrophosphate Cyclic AMP AMP OH OH O i
  • 31. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Many G-proteins – Trigger the formation of cAMP, which then acts as a second messenger in cellular pathways ATP GTP cAMP Protein kinase A Cellular responses G-protein-linked receptor Adenylyl cyclase G protein First messenger (signal molecule such as epinephrine) Figure 11.10
  • 32. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Calcium ions and Inositol Triphosphate (IP3) • Calcium, when released into the cytosol of a cell – Acts as a second messenger in many different pathways
  • 33. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Calcium is an important second messenger – Because cells are able to regulate its concentration in the cytosol EXTRACELLULAR FLUID Plasma membrane ATP CYTOSOL ATP Ca2+ pump Ca2+ pump Ca2+ pump Endoplasmic reticulum (ER) Nucleus Mitochondrion Key High [Ca2+] Low [Ca2+] Figure 11.11
  • 34. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Other second messengers such as inositol triphosphate and diacylglycerol – Can trigger an increase in calcium in the cytosol
  • 35. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 11.12 3 2 1 IP3 quickly diffuses through the cytosol and binds to an IP3– gated calcium channel in the ER membrane, causing it to open. 4 The calcium ions activate the next protein in one or more signaling pathways. 6 Calcium ions flow out of the ER (down their con- centration gradient), raising the Ca2+ level in the cytosol. 5 DAG functions as a second messenger in other pathways. Phospholipase C cleaves a plasma membrane phospholipid called PIP2 into DAG and IP3. A signal molecule binds to a receptor, leading to activation of phospholipase C. EXTRA- CELLULAR FLUID Signal molecule (first messenger) G protein G-protein-linked receptor Various proteins activated Endoplasmic reticulum (ER) Phospholipase C PIP2 IP3 (second messenger) DAG Cellular response GTP Ca2+ (second messenger) Ca2+ IP3-gated calcium channel
  • 36. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Concept 11.4: Response: Cell signaling leads to regulation of cytoplasmic activities or transcription
  • 37. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cytoplasmic and Nuclear Responses • In the cytoplasm – Signaling pathways regulate a variety of cellular activities
  • 38. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Cytoplasmic response to a signal Figure 11.13 Glucose-1-phosphate (108 molecules) Glycogen Active glycogen phosphorylase (106) Inactive glycogen phosphorylase Active phosphorylase kinase (105) Inactive phosphorylase kinase Inactive protein kinase A Active protein kinase A (104) ATP Cyclic AMP (104) Active adenylyl cyclase (102) Inactive adenylyl cyclase Inactive G protein Active G protein (102 molecules) Binding of epinephrine to G-protein-linked receptor (1 molecule) Transduction Response Reception
  • 39. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Other pathways – Regulate genes by activating transcription factors that turn genes on or off Reception Transduction Response mRNA NUCLEUS Gene P Active transcription factor Inactive transcription factor DNA Phosphorylation cascade CYTOPLASM Receptor Growth factor Figure 11.14
  • 40. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Fine-Tuning of the Response • Signal pathways with multiple steps – Can amplify the signal and contribute to the specificity of the response
  • 41. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Signal Amplification • Each protein in a signaling pathway – Amplifies the signal by activating multiple copies of the next component in the pathway
  • 42. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The Specificity of Cell Signaling • The different combinations of proteins in a cell – Give the cell great specificity in both the signals it detects and the responses it carries out
  • 43. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Pathway branching and “cross-talk” – Further help the cell coordinate incoming signals Response 1 Response 4 Response 5 Response 2 Response 3 Signal molecule Cell A. Pathway leads to a single response Cell B. Pathway branches, leading to two responses Cell C. Cross-talk occurs between two pathways Cell D. Different receptor leads to a different response Activation or inhibition Receptor Relay molecules Figure 11.15
  • 44. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Signaling Efficiency: Scaffolding Proteins and Signaling Complexes • Scaffolding proteins – Can increase the signal transduction efficiency Signal molecule Receptor Scaffolding protein Three different protein kinases Plasma membrane Figure 11.16
  • 45. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Termination of the Signal • Signal response is terminated quickly – By the reversal of ligand binding