Transcript bio4751Ch15-Part2W

Cell
Communication
Chapter 15Part I- General signaling strategies
Part II- G protein signaling
Part III- Enzyme-linked cell surface receptors
Part IV- Proteolysis-dependent signaling pathways
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 enzymelinked receptors
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
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- _________
INACTIVE G protein
1. Inactive state- a subunit bound
with ______
2. a, b and g subunits in one
complex
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. a subunit binds to and
______ a ____________
6. GTP on a subunit is
_________ to _____
7. a subunit __________
with b/g subunits
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
______
PATHWAY 1 - cAMP
What does cAMP look like??
1. ___________ produces ____
This is the “Target”
protein for the G- protein
designated ___
2. Note that ________ binds both __
and __ carbons of dATP ribose,
hence the name “________”
3. cAMP ___________ breaks
cAMP down to _______
Part II- G protein signaling
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
____________.
Part II- G protein signaling
PATHWAY 1 - cAMP
E. Examples of hormone-induced cell responses mediated by cAMP
Target tissue
Hormone
Major response
Muscle
___________
____________________
Heart
Fat
Ovary
__________
____________________
_____________
_________________
_________
__________
____________________
cAMP induction by serotonin
Red = High level cAMP
Yellow = Moderate level cAMP
Blue = Low level cAMP
Part II- G protein signaling
PATHWAY 2- Phospholipase C-b
F. Some examples of phospholipase C-b
cell responses- Smooth muscle
contraction, blood platelet
aggregation, glycogen breakdown
1. Signal molecule binds receptor
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
a. ____
Activates
protein
________
Release of Ca++
from
___________
____________
PI4,5-bisphosphate
b. ___
4. phospholipase C-b
breaks down _____
____________ into:
a. ______
b. _____
PATHWAY 2- Phospholipase C-b
Part II- G protein signaling
G. Overview of phospholipase C-b pathway ____activates
protein kinase C
(PKC)
___ binds a IP3gated __________
channel
Part II- G protein signaling
PATHWAY 2- Phospholipase C-b
H. We can activate these pathways with drugs
Drug
Effect
a. DAG
______________
____________
b. IP3
__________________ __________________
_____________________
Ca++ release via a non-G protein pathway: __________ interaction
I. Ca++ is a ubiquitous intracellular messenger
Part II- G protein signaling
a. Free Ca++ in cytoplasm is <____ M,
b. Extracellular is _____ M
c. Ca++-_______ pumps Ca++ out of cell and into ___
Example- Nerve cells_____________, influx of
Ca++, secretion of
____________________
How is the Ca++ signal transduced??
Through ______________
1. Ca++ binds ___________
2. This complex binds
______________
3. CaM kinases
______________ other
proteins
Part II- G protein signaling
One CaM kinase is important in ____________
If knock out _____________
in miceDefect in ____________
where things are 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.
2.
3.
4.
5.
6.
________ binds receptor
_____________ activated
________ produced
Gate opened
____ infux
Initiate __________ to
brain
____________ also use G-proteins
Termed “____“
operates through ______ production
K. How is a response _______________?
Part II- G protein signaling
____, _____ or other G-linked receptor kinases (______)
______________the receptor
________ then binds the phosphorylated receptor
• GTP converted to ____ on a subunit
• IP3 __________________
• Ca++ pumped ______
• cAMP _____________
Mechanisms of
inactivating
responses
Part II- G protein signaling
L. Summary
G-protein linked receptors act through G proteins
G protein
Gs
Gq
Golf
Gt
Target
Enzyme
_____________
_______________
Molecule
made
Target
_____
_____
____
__________,
__________
______
_______
_______________
_______
__________
__________
____________
_____
___________
_________
PKC, PKA and CaM kinases all phosphorylate target
proteins on________ or __________residues