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25,000 genes
Signal transduction-4000 genes (16 of genome)
320 cell types
700 Liver-specific genes
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Chapter 15-
Cell Communication
Part I- General signaling strategies
Part II- G protein signaling
Part III- Enzyme-linked cell surface receptors
Part IV- Proteolysis-dependent signaling pathways
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Outline
Part I- General signaling strategies
A. Two cell types
B. A typical signaling pathway
C. Most signaling molecules are hydrophilic
(water loving)
D. Some signaling molecules are hydrophobic
(water hating)
E. A review of membranes (from chapter 10)
F. Signaling over short or long distances
G. Autocrine signaling
H. Cells respond to specific combinations of
factors
I. Signaling through gap junctions
J. Different cells respond differently to the
same signal molecules
K. Nuclear receptors are ligand-activated gene
regulatory proteins
L. Three classes of cell-surface receptors
M. Common features of G protein-linked and
enzyme-linked receptors
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Chapter 15-
Cell Communication
Part I- General signaling strategies
A. Two cell types
1. Signaling cell

• Release
• Proteins
• ___________
• Amino acids
• _____________
• _____________
• Dissolved gases (CO, NO)

Most secreted by ___________ or _________
These are termed ________
2. Target cell
Respond by means of ___________
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Cell surface receptor pathways
BLA512 1/5/98 update
Enzyme-linked
Ion channel-linked No details shown
G-protein-linked
PDGF, EGF, IFa,b,and g, IL-2 ,IL-3, IL-4, IL-6
TNFa
TGF-b
PLCg
Grb2
Jak
G proteins
TRADD
Gs Golf
FADD
Gq Go
GNRPs (e.g. Sos)
TRAF
Ca from ER
Ras
IP3
PIP
Adenylyl cyclase
Cytoplasm
Raf (a MAPKKK)
DAG
PLCb
MAPKKK
MEKK (a MAPKKK)
NIK
cAMP
AMP
MAPKK (e.g.MEK)
PKC
JNKK
IKK
PKA
Caspases
MAPKKK
JNK
IkB/NFkB
MAP-kinase (ERK)
IkB/NFkB
p38
Cell death
Elk-1
jun
JNK
Gene
Gene
Nucleus
Gene
Gene
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LPS-mediated apoptosis Which pathway is
defective?
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Part I- General signaling strategies
B. A typical signaling pathway
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Part I- General signaling strategies
C. Most signaling molecules are __________ (water
loving)
Thus, cannot cross plasma membrane
D. Some signaling molecules are ______________
(water hating)
These may move easily through the plasma membrane
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Part I- General signaling strategies
E. A review of membranes (from chapter 10)
1. A typical membrane- a __________________ with
embedded __________________
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Part I- General signaling strategies
E. A review of membranes (from chapter 10)
2. A membrane phospholipid
________ head
____________ tail
Composed of fatty acids
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Part I- General signaling strategies
3. Membranes are composed of four major
_____________
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Part I- General signaling strategies
F. Signaling over short or long distances
1. __________________
2. _____________________
a. Paracrine- act locally
Requires _________ contact
Fast-acting, _________, high concentration
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2. Contact independent (continued)
Part I- General signaling strategies
b. ___________
c. _____________
Slow, _______________, low concentrations
Fast acting, ____________
e.g. hormones
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Part I- General signaling strategies
G. __________ signaling
Cell secretes signal molecules that bind back to
own _______
Function- _________ decisions made by a group of
cells.
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Part I- General signaling strategies
H. Signaling through ____________

• Small molecules are shared through these ports

• Ca, cAMP can pass, but not proteins or nucleic
  acids

I. Cells respond to specific ____________ of
factors
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Part I- General signaling strategies
J. Different cells respond differently to the
_______ signal molecules
Example- acetylcholine
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Part I- General signaling strategies
K. Nuclear receptors are _______________ gene
regulatory proteins
1. Ligands include

• ____________________- derived from cholesterol
• produced in adrenal, ovary, testis
• ________________- increase cell metabolism
• ______________ - from vitamin A impt. in
  development
• _________ (UV synthesizes) Regulates Ca
  metabolism

a. All are small, _________molecules carried by
_________proteins
b. Examples of signaling molecules that bind
_________ receptors
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Part I- General signaling strategies
K. Nuclear receptors are ligand-activated gene
regulatory proteins
c. Nuclear Receptors- belong to ______________
receptor superfamily
d. All have three domains
1. ____________________ domain
Interacts with ____________
2. ___________________ domain
3. __________________ domain
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Part I- General signaling strategies
K. Nuclear receptors are ligand-activated gene
regulatory proteins
e. Steroid hormones exhibit two response phases
1. _______ response
_________ response genes activated
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Part I- General signaling strategies
K. Nuclear receptors are ligand-activated gene
regulatory proteins
e. Steroid hormones exhibit two response phases
2. ________ secondary response
a. Primary response genes are ________ _______
b. Secondary response genes _______ _____
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L. Three classes of cell-surface receptors
Part I- General signaling strategies
1. _____________-linked - (Transmitter gated ion
channel)
Example- ______________
2. __________-linked Acts through a
________________________ _______________(G
protein)
All are ______ transmembrane proteins
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Part I- General signaling strategies
L. Three classes of cell-surface receptors
3. ___________-linked
Includes __________________
Most are ____________ transmembrane proteins
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M. Common features of G protein-linked and
enzyme-linked receptors
1. Both become active via ________________ 2.
Both use phosphorylation ______________ 3.
Phosphorylation occurs at _______, _____or
________residues 4. ___ of mammalian genes
encode these enzymes 5. Many are
__________________
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M. Common features of G protein-linked and
enzyme-linked receptors
6. These signaling complexes can either be on a
________________...
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M. Common features of G protein-linked and
enzyme-linked receptors
. Or ________________once the receptor is
activated.
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M. Common features of G protein-linked and
enzyme-linked receptors
7. Cells can respond ___________.
.or _________ to increasing signal molecules
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M. Common features of G protein-linked and
enzyme-linked receptors
8. Cellular memory
The response remains after the signal disappears
2. Activate a ___________________
Example- Muscle cell determination- Turn on
muscle-specific genes that regulate their own
expression
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Part I- General signaling strategies
9. Cells can also become ______________ to the
signal
How?

• Ligand binding cause ____________ of receptor
• Receptor ______________
• ______________ protein inactivated
• ______________ protein produced