Cell-to-cell communication primarily occurs through signal transduction pathways, involving multiple steps that amplify signals and result in cellular responses. These pathways often use protein phosphorylation and dephosphorylation as molecular switches and involve first and second messengers to relay signals within a cell. The effectiveness of these pathways can be fine-tuned through amplification, specificity, efficiency via scaffolding proteins, and signal termination.

1. CELL TO CELL COMMUNICATION
MIKG
FKG Usakti

2. Transduction: Cascades relay
signals
• Signal transduction involves multiple steps
• Multistep pathways can amplify a signal

3. Signal Transduction Pathways
• Receptor activates another protein, which
activates another, and so on, until protein
producing the response is activated
• At each step, the signal is transduced into a
different form, usually a shape change in a protein

4. Protein Phosphorylation and
Dephosphorylation
• In many pathways, the signal is transmitted by a
cascade of protein phosphorylations
• Protein kinases transfer phosphates from ATP to
protein, a process called phosphorylation

5. • Protein phosphatases remove the phosphates
from proteins, a process called dephosphorylation
• This phosphorylation and dephosphorylation
system acts as a molecular switch, turning
activities on and off or up or down, as required

6. Receptor
Signaling molecule
Activated relay
molecule
P
h
o
s
p
h
o
r
y
l
a
t
i
o
n
c
a
s
c
a
d
e
Inactive
protein kinase
1 Active
protein
kinase
1
Active
protein
kinase
2
Active
protein
kinase
3
Inactive
protein kinase
2
Inactive
protein kinase
3
Inactive
protein
Active
protein
Cellular
response
ATP
ADP
ATP
ADP
ATP
ADP
PP
PP
PP
P
P
P
P i
P i
P i

7. Activated relay
molecule
P
h
o
s
p
h
o
r
y
l
a
t
i
o
n
c
a
s
c
a
d
e
Inactive
protein kinase
1 Active
protein
kinase
1
Active
protein
kinase
2
Active
protein
kinase
3
Inactive
protein kinase
2
Inactive
protein kinase
3
Inactive
protein
Active
protein
ATP
ADP
ATP
ADP
ATP
ADP
PP
PP
PP
P
P
P i
P i
P i
P

8. Second Messengers
• The extracellular signal molecule (ligand) that
binds to the receptor is a pathway’s “first
messenger”
• Second messengers are small, nonprotein, water-
soluble molecules or ions that spread throughout a
cell
– Calcium
– cAMP

9. • Many signal molecules trigger formation of cAMP
• cAMP usually activates protein kinase A, which
phosphorylates various other proteins

10. G protein
First messenger
(signaling molecule
such as epinephrine)
G protein-coupled
receptor
Adenylyl
cyclase
Second
messenger
Cellular responses
Protein
kinase A
GTP
ATP
cAMP

11. Calcium Ions and Inositol Triphosphate (IP3)
• Calcium ions (Ca2+
) act as a second messenger in
many pathways
• Calcium is an important second messenger because
cells can regulate its concentration

12. G protein
EXTRA-
CELLULAR
FLUID
Signaling molecule
(first messenger)
G protein-coupled
receptor
Phospholipase C
DAG
PIP2
IP3
(second messenger)
IP3-gated
calcium channel
Endoplasmic
reticulum (ER)
CYTOSOL
Ca2
GTP

13. G protein
EXTRA-
CELLULAR
FLUID
Signaling molecule
(first messenger)
G protein-coupled
receptor
Phospholipase C
DAG
PIP2
IP3
(second messenger)
IP3-gated
calcium channel
Endoplasmic
reticulum (ER)
CYTOSOL
Ca2
(second
messenger)
Ca2
GTP

14. G protein
EXTRA-
CELLULAR
FLUID
Signaling molecule
(first messenger)
G protein-coupled
receptor
Phospholipase C
DAG
PIP2
IP3
(second messenger)
IP3-gated
calcium channel
Endoplasmic
reticulum (ER)
CYTOSOL
Various
proteins
activated
Cellular
responses
Ca2
(second
messenger)
Ca2
GTP

15. Nuclear and Cytoplasmic
Responses
• Ultimately, a signal transduction pathway leads to
regulation of one or more cellular activities
• Many signaling pathways regulate the synthesis of
enzymes or other proteins, usually by turning
genes on or off in the nucleus
• The final activated molecule in the signaling
pathway may function as a transcription factor

16. Growth factor
Receptor
Reception
Transduction
CYTOPLASM
Response
Inactive
transcription
factor
Active
transcription
factor
DNA
NUCLEUS mRNA
Gene
Phosphorylation
cascade
P

17. 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 cyclase
Active adenylyl cyclase (102
)
ATP
Cyclic AMP (104
)
Inactive protein kinase A
Active protein kinase A (104
)
Inactive phosphorylase kinase
Active phosphorylase kinase (105
)
Inactive glycogen phosphorylase
Active glycogen phosphorylase (106
)
Glycogen
Glucose 1-phosphate
(108
molecules)

18. Fine-Tuning of the Response
• There are four aspects of fine-tuning to consider
– Amplifying the signal (and thus the response)
– Specificity of the response
– Overall efficiency of response, enhanced by
scaffolding proteins
– Termination of the signal
Amplify: Cascade amplifies the cell response
At each step, the number of activated product is
greater than in the step before
Specify:
Different proteins allow cells to detect and respond
to different signals
Scaffolding:
Scaffolding proteins are large relay proteins to which
other relay proteins
Increase the signal transduction efficiency by grouping
together different proteins involved in the same pathway

19. Apoptosis integrates multiple cell-
signaling pathways
• Apoptosis is programmed or controlled cell
suicide
• Components of the cell are chopped up and
packaged into vesicles that are digested by
scavenger cells
• Apoptosis prevents enzymes from leaking out of a
dying cell and damaging neighboring cells

20. True / false
1. There is no fundamental distinction between
signaling molecules that bind to cell-surface
receptors and those that bind to intracellular
receptors
2. All second messengers are water soluble
and diffuse freely through the cytosol

21. EXPLAINING PROBLEMS
• how is it that different cells can respond in
different ways to exactly the same signaling
molecule even when the have identical
receptors
• Describe three ways in which a gradual
increase in an extracellular signal can be
sharpened by the target cell to produce an
abrupt or nearly all-or-non response