1. Cell Communication

2. Evolution of Cell Signaling
A signal-transduction pathway is a series of steps by which a signal on a cell’s surface is converted into a specific cellular response
Signal transduction pathways convert signals on a cell’s surface into cellular responses
Pathway similarities suggest that ancestral signaling molecules evolved in prokaryotes and have since been adopted by eukaryotes

3. Communication Between Mating Yeast Cells
 factor
Receptor
Exchange of mating factors.
Each cell type
secretes a
mating factor
that binds to
receptors on
the other cell
type.
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  cells.
Yeast cell,
mating type a
mating type  
a/ a 1 3 2

4. Cells Communication Direct contact Paracrine signaling
Endocrine signaling
Synaptic signaling

5. Direct Contact
Cells touch each other and signal molecules travel through special connections called communicating junctions
Communicating junctions link the cytoplasms of 2 cells together, permitting the controlled passage of small molecules or ions between them.
Plasma membranes
Gap junctions
between animal cells
Cell junctions
Cell-cell recognition
Plasmodesmata
between plant cells

6. Cell Communication In Animals
In many other cases, animal cells communicate using local regulators, messenger molecules that travel only short distances
In long-distance signaling, plants and animals use chemicals called hormones
(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.
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.
Local regulator
diffuses through
extracellular fluid
Secreting
cell
Target cell
Secretory
vesicle
Electrical signal
along nerve cell
triggers release of
neurotransmitter
Neurotransmitter
diffuses across synapse
is stimulated
Local signaling
Long-distance signaling
Endocrine cell
Blood
vessel
Target

7. Relay molecules in a signal transduction pathway
Cell Signaling
The cells of a organism communicate with each other by releasing signal molecules that bind to receptor proteins located either on or inside of target cells.
Three stages of cell signaling:
Reception - each target cell has receptors that detect a specific signal molecule and binds to it
Transduction – binding of the signal molecule changes the receptor protein in some way that initiates transduction or conversion of the signal to a form that can bring about a specific cellular response
Response – transduced signal triggers a specific cellular response, any cell activity
EXTRACELLULAR
FLUID
Receptor
Signal
molecule
Relay molecules in a signal transduction pathway
Plasma membrane
CYTOPLASM
Activation
of cellular
response
Reception
Transduction
Response 1 2 3

8. Reception
A signal molecule binds to a receptor protein, causing it to change shape
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

9. Receptors Intracellular receptors
Some signal molecules that are small or hydrophobic can pass through the plasma membrane and bind to receptors located inside the cell
Intracellular receptors are cytoplasmic or nuclear proteins
Cell surface receptors. - Signal molecules that cannot pass through the plasma membrane bind to receptors located on the surface of the membrane

10. Intracellular Receptors
Gene Regulators
Signal molecule joins to the receptor, the receptor changes shape and a DNA binding site is exposed.
The DNA binding site joins to a specific segment of DNA and activates (or suppresses) a particular gene
Enzyme Receptor
These receptors function as enzymes – proteins that catalyze (speed up) specific chemical reactions.
When a signal molecule joins to the receptor, the receptor’s catalytic domain is activated (or deactivated).

11. Steroid hormone interacting with an intracellular receptor
(testosterone)
EXTRACELLULAR
FLUID
Receptor
protein
Plasma
membrane
Hormone-
receptor
complex
DNA
mRNA
NUCLEUS
CYTOPLASM
New protein
The steroid
hormone testosterone
passes through the
plasma membrane. 1
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
The bound protein
stimulates the
transcription of
the gene into mRNA. 4
The mRNA is
translated into a
specific protein. 5

12. Surface Receptors
Receptors located on the surface of the membrane, 4 types:
Chemically gated ion channels
Enzymatic receptors
G-protein-linked receptors
Integrins

13. Chemically Gated Ion Channels
Gate close
Cellular response
Gate open
Gate close
Ligand-gated
ion channel receptor
Plasma Membrane
Signal molecule (ligand)
Gate
Closed
Ions
An ion channel receptor acts as a gate when the receptor changes shape
When a signal molecule binds as a ligand to the receptor, the gate allows specific ions, such as Na+ or Ca2+, through a channel in the receptor

14. Enzymatic Receptors
Embedded in the plasma membrane, with their catalytic site exposed inside the cell.
Catalytic site activated when the signal molecule joins to the receptor.
Function as protein kinases (enzymes that phosphorylate proteins.)

15. Receptor Tyrosine Kinases
Signal molecule
Signal-binding site
CYTOPLASM
Tyrosines
Signal molecule
 Helix in the
Membrane
Tyr
Dimer
Receptor tyrosine kinase proteins (inactive monomers) 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
6 ATP ADP

16. G-protein-linked Receptors
Signal molecule joins to a receptor, the receptor activates a G protein
The activated G protein can then activate an ion channel or enzyme in the plasma membrane.
G protein
Activated
Enzyme or
ion channel
enzyme or
G-protein-linked receptor
Signal

17. G-PROTEIN-LINKED RECEPTORS
Signal-binding site
G-PROTEIN-LINKED RECEPTORS
G-protein-linked
receptor
Plasma Membrane
Enzyme
G-protein (inactive)
CYTOPLASM
Cellular response
Activated
enzyme
Activated receptor
Signal molecule
Inactive
Segment that
interacts with
G proteins
GDP
GTP
P i

18. Second Messengers
Some enzymatic receptors and most G-protein-linked receptors relay their message into the cell by activating other molecules or ions inside the cell.
These molecules and ions, called second messengers, transmit the message within the cell. The 2 most common second messengers are cAMP and Ca++

19. Signal Transduction Pathways
Transduction usually involves multiple steps
Multistep pathways
Can amplify a signal
Provide more opportunities for coordination and regulation
The molecules that relay a signal from receptor to response are mostly proteins
The receptor activates another protein, which activates another, and so on, until the protein producing the response is activated
At each step, the signal is transduced into a different form, usually a conformational change

20. A Phosphorylation Cascade
In many pathways, the signal is transmitted by a cascade of protein phosphorylations - phosphatase enzymes remove the phosphates
This phosphorylation and dephosphorylation system acts as a molecular switch, turning activities on and off
Signal molecule
Active
protein
kinase 1 2 3
Inactive
protein kinase
Cellular
response
Receptor P P 
ATP
ADP PP
Activated relay
molecule
A relay molecule
activates protein kinase 1.
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.
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 i
Phosphorylation cascade

21. cAMP Second Messenger G-protein-signaling pathway
First messenger
(signal molecule
such as epinephrine)
ATP
GTP
cAMP
Protein
kinase A
Cellular responses
G-protein-linked
receptor
Adenylyl
cyclase
G protein
Second
messenger
Signal molecule binds to surface receptor
Surface receptor activates a G protein
G protein activates the membrane-bound enzyme, adenylyl cyclase
Adenylyl cyclase catalyzes synthesis of camp, which binds to a target protein
Target protein initiates cellular change

22. Cyclic AMP
Cyclic AMP (cAMP) is one of the most widely used second messengers
Adenylyl cyclase, an enzyme in the plasma membrane, converts ATP to cAMP in response to an extracellular signal O –O N O P OH
CH2
NH2
ATP
Ch2
H2O HO
Adenylyl cyclase
Phoshodiesterase
Pyrophosphate
Cyclic AMP
AMP i

23. Cyclic AMP Pathway

24. Calcium (Ca++) Pathways
Calcium ions (Ca2+) act as a second messenger in many pathways
Calcium is an important second messenger because cells can regulate its concentration
ATP
EXTRACELLULAR
FLUID
Mitochondrion
Ca2+
pump
Plasma
membrane
CYTOSOL
Endoplasmic
reticulum (ER)
High [Ca2+]
Key
Nucleus
Low [Ca2+]

25. Calcium ions and Inositol Triphosphate (IP3)
A signal transduction pathway may trigger an increase in calcium in the cytosol
Pathways leading to the release of calcium involve inositol triphosphate (IP3) and diacylglycerol (DAG) as second messengers

26. Ca++ Pathway Signal molecule binds to surface receptor
Surface receptor activates a G protein
G protein activates the membrane-bound enzyme, phospholipase C
Phospholipase C catalyzes synthesis of inositol triphosphate, which stimulates release of Ca++ from ER
Released Ca++ initiates cellular change

27. Calcium and IP3 in signaling pathways2 3
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.
EXTRA-
CELLULAR
FLUID
Signal molecule
(first messenger)
G protein
G-protein-linked
receptor
Various
proteins
activated
Endoplasmic
reticulum (ER)
Phospholipase C
PIP2
IP3
DAG
Cellular responses
GTP
Ca2+
(second
messenger)
IP3-gated
calcium channel
A signal molecule binds
to a receptor, leading to
activation of phospholipase C. 1
CYTOSOL

28. Fine-Tuning of the Response
Multistep pathways have two important benefits:
Amplifying the signal (and thus the response)
Contributing to the specificity of the response
Enzyme cascades amplify the cell’s response
At each step, the number of activated products is much greater than in the preceding step

29. Amplification
Due to the many steps in the cell signaling process, one signal molecule can trigger a “cascade” effect

30. Binding of epinephrine to G-protein-linked receptor (1 molecule)
Cytoplasmic response to a signal: the stimulation of glycogen breakdown by epinephrine
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

31. Specificity of Cell Signaling
molecule
Receptor
Relay
molecules
Response 1
Response 2
Response 3
Cell B. Pathway branches,
leading to two responses
Cell A. Pathway leads
to a single response
Cell C. Cross-talk occurs
between two pathways
Response 4
Response 5
Activation
or inhibition
Cell D. Different receptor
leads to a different response
Different kinds of cells have different collections of proteins
These differences in proteins give each kind of cell specificity in detecting and responding to signals
The response of a cell to a signal depends on the cell’s particular collection of proteins
Pathway branching and “cross-talk” further help the cell coordinate incoming signals

32. Signaling Efficiency: Scaffolding Proteins and Signaling Complexes
Rather than relying on diffusion of large relay molecules such as proteins, many signal pathways are linked together physically by scaffolding proteins.
Scaffolding proteins may themselves be relay proteins to which several other relay proteins attach.
This hardwiring enhances the speed, accuracy, and efficiency of signal transfer between cells.
Signal molecule
Receptor
Scaffolding protein
Three different protein kinases
Plasma membrane
Figure 11.16