ap biologyminzenmayer cell communication. cell signaling a signal transduction pathway is a series...
TRANSCRIPT
Minzenmayer
Cell Signaling A signal transduction pathway is a series of
steps by which a signal on a cell’s surface is converted into a specific cellular response
Signal transduction pathways convert signals on a cell’s surface into cellular responses
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Local vs. Long Distance Signaling Animal cells communicate using local
regulatorsmessenger molecules that travel only short distances
long-distance signalingplants and animals use chemicals called hormones
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e.g., interferon release by viral-infected cells
Local Signaling w/o Direct Contact
Paracrine Signaling Synaptic Signaling
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Lo
ng
-Dis
tan
ce D
iffu
sio
n Note how specificity is determined by presence/absence of receptor protein
Fig. 11-6-1
Reception1
EXTRACELLULARFLUID
Receptor
Signalingmolecule
Plasma membrane
CYTOPLASM
1
Signal Transduction
Fig. 11-6-2
Reception1
EXTRACELLULARFLUID
Receptor
Signalingmolecule
Plasma membrane
CYTOPLASM
1
Relay molecules in a signal transduction pathway
Transduction2
Signal Transduction
Fig. 11-6-3
EXTRACELLULARFLUID
Plasma membrane
CYTOPLASM
Receptor
Signalingmolecule
Relay molecules in a signal transduction pathway
Activationof cellularresponse
Reception Transduction Response1 2 3
Signal Transduction
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Signal Transduction
In this case the receptor protein is a membrane proteinLigan
d
Often turning on or off enzyme activity
What’s the point of Cell Communication??
Examples: Epinephrine stimulates the breakdown of
glycogen in mammals Temperature determines sex of some
vertebrate organisms DNA repair mechanisms
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Receptors in Plasma Membrane three main types of membrane receptors:
G protein-coupled receptorsReceptor tyrosine kinasesIon channel receptors
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STEP 1: RECEPTION
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G Proteins G protein-coupled receptor
plasma membrane receptor that works with the help of a G protein
G protein acts as an on/off switch: If GDP is bound to the G protein, G protein is inactive
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Fig. 11-7b
G protein-coupledreceptor
Plasmamembrane
EnzymeG protein(inactive)
GDP
CYTOPLASM
Activatedenzyme
GTP
Cellular response
GDP
P i
Activatedreceptor
GDP GTP
Signaling molecule
Inactiveenzyme
1 2
3 4
G-Protein-Linked ReceptorThe more ligand binding, the greater the cellular response
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Tyrosine Kinases Receptor tyrosine kinases
membrane receptors that attach phosphates to tyrosines
can trigger multiple signal transduction pathways at once
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tein
Kin
ase
& P
ho
sph
atas
eP r o te in O H + A T P P r o te in O P
O
O
O
+ A D P
P i H 2 O
P r o te in K in a s e
P r o te in P h o s p h a t a s e
reversibility of phosphorylation makes signaling
reversible
responses tend to
continue (or expand) only
so long as signaling continues
reversibility contributes
to the dynamic nature of
cells
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Tyrosine Kinase Receptor
Lig
an
d R
ece
pti
on
Re
cep
tor
dim
eri
zati
on
Ph
osp
ho
ryliz
atio
n
Protein
Activation
Tra
ns
du
ctio
n
Re
sp
on
se
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Ligand Gated Ion Channel ligand-gated ion channel receptor
acts as gate when receptor changes shape
When signal molecule binds as a ligand to receptor, gate allows specific ions, such as Na+ or Ca2+, through a channel in receptor
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Ion
-Ch
ann
el R
ecep
tor
Reversibility is assured by pumping ions
back out again (using
separate protein)
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Wrap-Up
Would a hydrophobic molecule be expected to
have an internal or membrane receptor?
Modeling Reception Work in groups of 3-4 Choose either G-Protein System or
Tyrosine-Kinase Receptor System Build a model Film your group “acting out” model –
think of this as a tutorial video for peers Email video to
[email protected] Best videos will be uploaded to website
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Modeling Reception Use rest of class period today/finish after
school GOAL: model TODAY; film Friday Film due Friday @ end of class Questions due MONDAY 1/12/14
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Intracellular Receptors Some receptor proteins are intracellular
found in cytosol or nucleus of target cells
Examples of messengers steroid and thyroid hormones of animals
An activated hormone-receptor complex can act as a transcription factor
turning on specific genes
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Fig. 11-8-1
Hormone(testosterone)
Receptorprotein
Plasmamembrane
EXTRACELLULARFLUID
DNA
NUCLEUS
CYTOPLASM
Intr
acel
lula
r R
ecep
tor
Fig. 11-8-2
Receptorprotein
Hormone(testosterone)
EXTRACELLULARFLUID
Plasmamembrane
Hormone-receptorcomplex
DNA
NUCLEUS
CYTOPLASM
Intr
acel
lula
r R
ecep
tor
Fig. 11-8-3
Hormone(testosterone)
EXTRACELLULARFLUID
Receptorprotein
Plasmamembrane
Hormone-receptorcomplex
DNA
NUCLEUS
CYTOPLASM
Intr
acel
lula
r R
ecep
tor
Fig. 11-8-4
Hormone(testosterone)
EXTRACELLULARFLUID
PlasmamembraneReceptor
protein
Hormone-receptorcomplex
DNA
mRNA
NUCLEUS
CYTOPLASM
Intr
acel
lula
r R
ecep
tor
Fig. 11-8-5
Hormone(testosterone)
EXTRACELLULARFLUID
Receptorprotein
Plasmamembrane
Hormone-receptorcomplex
DNA
mRNA
NUCLEUS New protein
CYTOPLASM
Intr
acel
lula
r R
ecep
tor
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Transduction molecules that relay a signal from
receptor to response are mostly proteins Like falling dominoes, receptor activates
another protein, which activates another, …..until protein producing response is activated
At each step, signal is transduced into a different form, usually a shape change in a protein
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Protein Phosphorylation & Dephosphorylation
In many pathways, signal is transmitted by cascade of protein phosphorylations
Protein kinases transfer phosphates from ATP to protein, a process called phosphorylation
Protein phosphatases remove phosphates from proteins, a process called dephosphorylation
phosphorylation and dephosphorylation system acts as molecular switch, turning activities on and off
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Signaling molecule
Receptor Activated relaymolecule
Inactiveprotein kinase1
Activeproteinkinase1
Inactiveprotein kinase2
ATPADP
Activeproteinkinase2
P
PPP
Inactiveprotein kinase3
ATPADP Active
proteinkinase3
P
PPP
i
ATPADP P
ActiveproteinPP
P i
Inactiveprotein
Cellularresponse
Phosphorylation cascade
i
Phosphorylation Cascade
Activates protein kinase
Active PK1 transfers PFrom ATP to inactive PK2
Protein phosphatases (PP) catalyze removal of P to make them inactive again
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Small Molecules & Ions Second Messengers
extracellular signal molecule that binds to receptor is a pathway’s “first messenger”
Second messengers are small, nonprotein, water-soluble molecules or
ions that spread throughout a cell by diffusion
participate in pathways initiated by G protein-coupled receptors and receptor tyrosine kinases
Cyclic AMP and calcium ions are common second messengers
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Cyclic AMP cAMP
widely used second messengers Adenylyl cyclase
converts ATP to cAMP in response to extracellular signal
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cAMP Many signal molecules trigger formation of cAMP Other components of cAMP pathways are
G proteins
G protein-coupled receptors
protein kinases
cAMP usually activates protein kinase A, which phosphorylates various other proteins
Further regulation of cell metabolism is provided by G-protein systems that inhibit adenylyl cyclase
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First messengerFig. 11-11
G protein
Adenylylcyclase
GTP
ATP
cAMPSecondmessenger
Proteinkinase A
G protein-coupledreceptor
Cellular responses
cAM
P a
s a
2nd
Mes
sen
ger
Cell Signaling - Disease Cholera
Caused by Vibrio cholerae in contaminated waterToxin secreted by V. cholerae in small intestineToxin modifies G protein involved in salt/water secretion
Can no longer hydrolyze GTPAlways active - stimulates cAMP production
Intestinal cells secrete water/ionsSevere diarrhea
often lethal due to dehydration and salt imbalance
Cell Signaling - Cholera
H2O, ions
H2O, ionsGDPGTP
Toxinactive inactive
Intestinal Cell
Ext
Int
Net Effect
Copyright © 2005 Pearson Education, Inc., publishing as Benjamin Cummings
cAMP
Intestinal Lumen
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Calcium Ions & Inositol Triphosphate (IP3)
Calcium ions (Ca2+) act as a second messenger in many pathways
Calcium is an important second messenger because cells can regulate its concentration
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Nuclear & Cytoplasmic Responses signal transduction pathway leads to
regulation of one or more cellular activities response may occur in
cytoplasm or may involve action in nucleus
Many signaling pathways regulate synthesis of proteins
usually by turning genes on or off in nucleus final activated molecule may function as
transcription factor
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Fig. 11-14Growth factor
Receptor
Phosphorylationcascade
Reception
Transduction
Activetranscriptionfactor
ResponseP
Inactivetranscriptionfactor
CYTOPLASM
DNA
NUCLEUS mRNA
GeneNu
clea
r R
esp
on
se
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Fine Tuning Response Multistep pathways have two important
benefits:Amplifying signal
and therefore the response
Contributing to specificity of response Signal Amplification
Enzyme cascades amplify cell’s response
At each step, number of activated products is much greater than in preceding step
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