Cell Communication

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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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Part II- G protein signaling
A. G protein-linked receptors
B. Trimeric GTP-binding proteins (G proteins)
relay the signal
C. Steps to activate a G protein
PATHWAY 1 - cAMP
D. cAMP-mediated transduction
E. Examples of hormone-induced cell responses
mediated by cAMP
F. Some examples of phospholipase C-b cell
responses-
PATHWAY 2- Phospholipase C-b
G. Overview of phospholipase C-b pathway
H. We can activate these pathways with drugs
I. Ca is a ubiquitous intracellular messenger
J. G-protein linked receptors required for vision
and smell
K. How is a response desensitized?
L. Summary
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Part II- G protein signaling
A. G protein-linked receptors

• ______ membrane proteins
• __ of C. nematode genes
• _____ G proteins used for
• _____ in mice
• Activated by ___________
• __________,____________

B. Trimeric GTP-binding proteins (_______) relay
the signal
Three subunits- _________

1. Inactive state- a subunit bound with ______
2. a, b and g subunits in one complex

INACTIVE G protein
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Part II- G protein signaling
C. Steps to activate a G protein
1. Signal molecule binds ____________
2. G protein _________ with receptor
3. GDP is replaced by _____ on __ subunit
4. ____ proteins dissociate from __ subunit
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Part II- G protein signaling
5. a subunit binds to and ______ a ____________
6. GTP on a subunit is _________ to _____
7. a subunit __________ with b/g subunits
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Part II- G protein signaling
PATHWAY 1 - cAMP
D. cAMP-mediated transduction
1. Signal molecule binds _________
2. G protein interacts with receptor, ____ is
replaced by ____, and _________ dissociate from a
subunit
G protein is termed __ in this pathway
3. A subunit interacts with ___________________
4. ____ is converted to ______
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PATHWAY 1 - cAMP
Part II- G protein signaling
What does cAMP look like??
1. ___________ produces ____
This is the Target protein for the G- protein
designated ___
3. cAMP ___________ breaks cAMP down to _______
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PATHWAY 1 - cAMP
Part II- G protein signaling
5. cAMP binds ____________________ (PKA)

• PKA action likely accounts for all ___________
  effects
• PKA is composed of _______________ subunits and
  _____ __________ subunits

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PATHWAY 1 - cAMP
Part II- G protein signaling
7. Activated PKA is transported into
______________.
8. PKA_____________ CRE-binding protein (______).
9. CREB interacts with cofactor ____, which
activates gene ____________.
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PATHWAY 1 - cAMP
Part II- G protein signaling
E. Examples of hormone-induced cell responses
mediated by cAMP
Target tissue
Hormone
Major response
Muscle
___________
____________________
__________
____________________
Heart
Fat
_____________
_________________
Ovary
_________ __________
____________________
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PATHWAY 2- Phospholipase C-b
Part II- G protein signaling
1. Signal molecule binds receptor
F. Some examples of phospholipase C-b cell
responses- Smooth muscle contraction, blood
platelet aggregation, glycogen breakdown
2. G protein interacts with receptor, GDP is
replaced by GTP, and b/g proteins dissociate from
a subunit
G protein is termed __ in this pathway
3. __activates phospholipase C-b
4. phospholipase C-b breaks down _____
____________ into
Activates protein ________
a. ____
Release of Ca from ___________ ____________
a. ______
PI4,5-bisphosphate
b. _____
b. ___
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PATHWAY 2- Phospholipase C-b
Part II- G protein signaling
G. Overview of phospholipase C-b pathway
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PATHWAY 2- Phospholipase C-b
Part II- G protein signaling
H. We can activate these pathways with drugs
Drug
Effect
a. DAG
______________
____________
b. IP3
__________________ _____________________
__________________
Ca release via a non-G protein pathway
__________ interaction
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I. Ca is a ubiquitous intracellular messenger
Part II- G protein signaling
a. Free Ca in cytoplasm is lt____ M,
b. Extracellular is _____ M
c. Ca-_______ pumps Ca out of cell and into
___
Example- Nerve cells- _____________, influx of
Ca, secretion of ____________________
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How is the Ca signal transduced??
Through ______________
1. Ca binds ___________
2. This complex binds ______________
3. CaM kinases ______________ other proteins
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Part II- G protein signaling
One CaM kinase is important in ____________
If knock out _____________ in mice-
Defect in ____________ where things are in _____
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Part II- G protein signaling
J. G-protein linked receptors required for ______
and _______
Humans- distinguish gt__________ distinct smells
How?- by 1000s of __________ olfactory receptors
(____)

1. ________ binds receptor
2. _____________ activated
3. ________ produced
4. Gate opened
5. ____ infux
6. Initiate __________ to brain

____________ also use G-proteins
Termed ____
operates through ______ production
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K. How is a response _______________?
Part II- G protein signaling
____, _____ or other G-linked receptor kinases
(______) ______________the receptor

• GTP converted to ____ on a subunit
• IP3 __________________
• Ca pumped ______
• cAMP _____________

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L. Summary
Part II- G protein signaling
G-protein linked receptors act through G proteins
Target Enzyme
Molecule made
G protein
Target
Gs
_____
_____________
_____
__________, __________
Gq
_______________
____
______
_______
Golf
_______
_______________
__________
Gt
__________ ____________
_____ _________
___________
PKC, PKA and CaM kinases all phosphorylate target
proteins on________ or __________residues