Download Part I- Overview

www.ux1.eiu.edu/~cfgab
www.ux1.eiu.edu/~cfgab
Lectures saved
as Html files..
…and
powerpoint files
Click on “Part I-Overview“
If you have Microsoft Powerpoint:
-You can print out the lectures 6 slides /page
To print1. Select File- Print
2. In the pop-up window, select…
Slides
Handouts
Pure black
and white
“6” slides per page
OK
Signal transduction~4000 genes (16 % of
genome)
25,000 genes
Signaling molecules
376(1.2%)
Receptors1540 (5%)
Kinases- 868
(2.8%)
Other components968 (3.2%)
320 cell types
700 Liver-specific genes
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
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
Cell
Communication
Chapter 15Part I- General signaling strategies
A. Two cell types
1. Signaling cell
Release
Most secreted by
•Proteins
___________ or
•___________
_________
•Amino acids
•_____________
•_____________
•Dissolved gases (CO, NO)
These are termed ________
2. Target cell
Respond by means of ___________
BLA512 1/5/98 update
Cell surface receptor pathways
Enzyme-linked
Ion channel-linked G-protein-linked
No details shown
PDGF, EGF, IFa,b,and g,
IL-2 ,IL-3, IL-4, IL-6
TNFa
TGF-b
PLCg
Grb2 Jak
G proteins
Gs
Golf
Gq
Go
Ca++ from ER
PIP
Adenylyl cyclase
PLCb
AMP
GNRPs
(e.g. Sos)
Ras
IP3
(a MAPKKK)
cAMP
PKC
MAPKKK
MEKK
STAT
JNK
IkB/NFkB MAP-kinase (ERK)
Caspases
IkB/NFkB
p38
Elk-1
NIK
IKK
JNKK
MAPKKK
P
Smad
(a MAPKKK)
MAPKK
(e.g.MEK)
PKA
TRADD
FADD
TRAF
STAT
Raf
DAG
Smad
Cell death
jun
CREB
JNK
Gene
Fos
jun
AP1
NFkB
Gene
P
Elk-1
Nucleus
STAT
STAT
Fos
Gene
jun
AP1
Smad
Smad
Gene
Gene
LPS-mediated apoptosis: Which pathway is defective?
LPB
LPS
FasL
TNF
TNFR
FasR
FADD
Caspase 8
Sorb.
CD14
RIP
TRAF2
JNKK
p65
p105
c-jun
FADD
Caspase 8
P38 MAPK
NIK
MEKK1, 2, 3
JNK
IL1R1
TRADD
P38 MAPK
TPL-2
TLR-4
Calyculin A,
Okadaic Acid
PDTC
TAK1
TRAF6
MyD88
IRAK
TNF
PKC
EGFR
IKK
MEK
PD098059
ERK1,2
ALLN, HMA
IkB
NF-kB
P105 phos, degraded
TGFBR
SN50
Apoptosis
Proteasome
NF-kB-responsive genes
A1, A20, ,Fas, FasL,TNF, Bcl2,
TRAF1,2, c-IAP1,2
ROS
Part I- General signaling strategies
B. A typical
signaling pathway
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
Part I- General signaling strategies
E. A review of membranes (from chapter 10)
1. A typical membrane- a __________________ with
embedded __________________
Part I- General signaling strategies
E. A review of membranes (from chapter 10)
2. A membrane phospholipid
________ head
____________ tail
Composed of fatty acids
Part I- General signaling strategies
3. Membranes are
composed of four
major _____________
Part I- General signaling strategies
F. Signaling over short or long distances
1. __________________
Requires _________ contact
2. _____________________
a. Paracrine- act locally
Fast-acting, _________,
high concentration
2. Contact independent (continued)
b. ___________
Fast acting, ____________
Part I- General signaling strategies
c. _____________
Slow, _______________,
low concentrations
e.g. hormones
Part I- General signaling strategies
G. __________ signaling
Cell secretes signal molecules that bind back to own _______
Function- _________ decisions made by a group of cells.
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
Part I- General signaling strategies
J. Different cells respond differently to the
_______ signal molecules
Example- acetylcholine
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
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
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
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
_______ _____
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
Part I- General signaling strategies
L. Three classes of cell-surface receptors
3. ___________-linked
Includes __________________
Most are ____________ transmembrane proteins
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 “__________________”
M. Common features of G protein-linked and enzyme-linked receptors
6. These signaling complexes can either be on a ________________...
M. Common features of G protein-linked and enzyme-linked receptors
…. Or ________________once the receptor is activated.
M. Common features of G protein-linked and enzyme-linked receptors
7. Cells can respond ___________….
….or _________ to increasing
signal molecules
Conc. of effector molecules
M. Common features of G protein-linked and enzyme-linked receptors
8. Cellular memory
The response remains after the
signal disappears
How?
1. The ________ activates the receptor
2. Activate a ___________________
Example- Muscle cell determinationTurn on muscle-specific genes that
regulate their own expression
Part I- General signaling strategies
9. Cells can also become ______________ to the signal
How?
•Ligand binding cause ____________ of receptor
•Receptor ______________
•______________ protein inactivated
•______________ protein produced