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
Outline
A. Two cell types
Part I- General signaling strategies
B. A typical signaling pathwayC. 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 distancesG. Autocrine signalingH. Cells respond to specific combinations of factorsI. Signaling through gap junctionsJ. Different cells respond differently to the same signal moleculesK. Nuclear receptors are ligand-activated gene regulatory proteins L. Three classes of cell-surface receptorsM. Common features of G protein-linked and enzyme-linked receptors
Part II- G protein signaling
B. Trimeric GTP-binding proteins (G proteins) relay the signal
A. G protein-linked receptors
C. Steps to activate a G protein
D. cAMP-mediated transduction
E. Examples of hormone-induced cell responses mediated by cAMP
F. Some examples of phospholipase C- cell responses-
G. Overview of phospholipase C-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
PATHWAY 1 - cAMP
PATHWAY 2- Phospholipase C-
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. and subunits in one complex
INACTIVE G protein
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
Part II- G protein signaling
5. subunit binds to and ______ a ____________
6. GTP on subunit is _________ to _____
7. subunit __________ with subunits
Part II- G protein signaling
D. cAMP-mediated transduction1. Signal molecule binds
_________
2. G protein interacts with receptor, ____ is replaced by ____, and dissociate from subunit
3. A subunit interacts with ___________________
4. ____ is converted to ______
G protein is termed “__” in this pathway
PATHWAY 1 - cAMPPart II- G protein signaling
What does cAMP look like??
2. Note that ________ binds both __ and __ carbons of dATP ribose, hence the name “________”
1. ___________ produces ____
3. cAMP ___________ breaks cAMP down to _______
This is the “Target” protein for the G- protein designated ___
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
6. Binding of cAMP causes active subunits to __________ and become “___________”
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 ____________.
PATHWAY 1 - cAMP Part II- G protein signaling
cAMP induction by serotonin
= High level cAMPRed
= Moderate level cAMPYellow
= Low level cAMPBlue
E. Examples of hormone-induced cell responses mediated by cAMP
Muscle ___________ ____________________
Heart __________ ____________________
Fat _____________ _________________
Ovary _________ __________
____________________
Target tissue Hormone Major response
PATHWAY 1 - cAMP Part II- G protein signaling
PATHWAY 2- Phospholipase C-F. Some examples of phospholipase C-
cell responses- Smooth muscle contraction, blood platelet aggregation, glycogen breakdown
PI4,5-bisphosphatea. ______
3. __activates phospholipase C-
4. phospholipase C-breaks down _____ ____________ into:
b. ___
a. ____
b. _____
Activates protein ________
Release of Ca++ from ___________ ____________
1. Signal molecule binds receptor
2. G protein interacts with receptor, GDP is replaced by GTP, and proteins dissociate from subunit
G protein is termed “__” in this pathway
Part II- G protein signaling
___ binds a IP3-gated __________ channel
G. Overview of phospholipase C-pathway ____activates protein kinase C (PKC)
PATHWAY 2- Phospholipase C- Part II- G protein signaling
H. We can activate these pathways with drugs
a. DAG
b. IP3 __________________ _____________________
PATHWAY 2- Phospholipase C-
______________Drug Effect
____________
__________________
Ca++ release via a non-G protein pathway: __________ interaction
Part II- G protein signaling
I. Ca++ is a ubiquitous intracellular messenger
a. Free Ca++ in cytoplasm is <____ M,
Example- Nerve cells- _____________, influx of Ca++, secretion of ____________________
Part II- G protein signaling
b. Extracellular is _____ M
c. Ca++-_______ pumps Ca++ out of cell and into ___
How is the Ca++ signal transduced??
Through ______________
1. Ca++ binds ___________
2. This complex binds ______________
3. CaM kinases ______________ other proteins
If knock out _____________ in mice-
Defect in ____________ where things are in _____
One CaM kinase is important in ____________Part II- G protein signaling
J. G-protein linked receptors required for ______ and _______
Humans- distinguish >__________ distinct smells
How?- by 1000s of __________ olfactory receptors (____)
1. ________ binds receptor2. _____________ activated3. ________ produced4. Gate opened5. ____ infux6. Initiate __________ to
brain
____________ also use G-proteins
Termed “____“
Part II- G protein signaling
operates through ______ production
K. How is a response _______________?
____, _____ or other G-linked receptor kinases (______) ______________the receptor
________ then binds the phosphorylated receptor
• GTP converted to ____ on subunit• IP3 __________________• Ca++ pumped ______• cAMP _____________
Mechanisms of inactivating responses
Part II- G protein signaling
L. SummaryG-protein linked receptors act through G proteins
Gs
Gq
__________________ _____
_______________ ____
______ _______
__________, __________
Golf ______________________ __________
Gt __________ ____________
_____ _________
___________
Target Enzyme
G protein Molecule made Target
PKC, PKA and CaM kinases all phosphorylate target proteins on________ or __________residues
Part II- G protein signaling