Receptor - Faperta UGM

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Signal Transduction
Pathways
“From
signal to gene expression”
Signal Transduction Pathways
The biochemical events that conduct the signal of a
hormone or growth factor from the cell exterior,
through the cell membrane and into the cytoplasm
which involve a number of molecules including
receptors, proteins, and messengers
a series of steps by which a signal on a cell’s surface
is converted into a specific cellular response
Overview on Plant Signal
Transduction
1. The stream of signals to which plant cells react is
continuous and complex
2. Signal transduction uses a network of interactions
within cells, and throughout the plants
Analogy view of
cell signaling transduction pathway
Input
(command)
Keyboard
Signal
perception
Endogenous:
phytohormone
Exogenous:
environmental cue
CPU
(Central Processing
Unit)
Chip
Signal Transduction
Network
Compiling,
Integration,
processing
Output
(performance)
Printer
Signal
Response
 Morphogenesis
change,
Growth development
differentiation
EXTRACELLULAR
FLUID
Reception
Transduction
Plasma membrane
Receptor
Signal
molecule
CYTOPLASM
EXTRACELLULAR
FLUID
Reception
Transduction
Plasma membrane
CYTOPLASM
Receptor
Relay molecules in a signal transduction
pathway
Signal
molecule
EXTRACELLULAR
FLUID
Reception
Transduction
Plasma membrane
CYTOPLASM
Response
Receptor
Activation
of cellular
response
Relay molecules in a signal transduction
pathway
Signal
molecule
Overview on Plant Signal
Transduction
1. The stream of signals to which plant cells react is
continuous and complex
2. Signal transduction uses a network of interactions
within cells, and throughout the plants
Signal transduction
(Simplified model)
STIMULUS
Ca2+
Plasma
membrane
R
Ca2+
Phos
Kin
Nuclear
membrane
R
TF
DNA
Signal Transduction
Components
Stimulus
Hormones, physical environment, pathogens
Receptor
On the plasmamembrane, or internal
Secondary messengers
Ca2+, G-proteins, Inositol Phosphate
Effector molecules
Protein kinases or phosphatases
Transcription factors
Response
Stomatal closure
Change in growth direction
STIMULUS
How many signal factors which
Plant will respond to?
--biotic and abiotic factors--
Stimulus
Reception
A signal molecule binds to a receptor protein, causing it to
change shape
The binding between a signal molecule (ligand)
and receptor is highly specific
– A conformational change in a receptor is often the
initial transduction of the signal
– Most signal receptors are plasma membrane proteins
Intracellular Receptors
• Some intracellular receptor proteins are found in
the cytosol or nucleus of target cells
• Small or hydrophobic chemical messengers can
readily cross the membrane and activate receptors
• An activated hormone-receptor complex can act
as a transcription factor, turning on specific
genes
Receptors in the Plasma
Membrane
• Most water-soluble signal molecules bind to
specific sites on receptor proteins in the plasma
membrane
• There are three main types of membrane
receptors:
1. G-protein-linked receptors
2. Receptor tyrosine kinases
3. Ion channel receptors
G-protein-linked Receptor
• It is a plasma membrane receptor that works
with the help of a G protein
• The G-protein acts as an on/off switch
• If GDP is bound to the G protein, the G protein
is inactive
Signal-binding site
Segment that
interacts with
G proteins
G-protein-linked receptor
Receptor Tyrosine Kinases
• Regulates cell growth and cell reproduction
• Tyrosine kinase catalyzes transfer of phosphate
group from ATP to tyrosines
• Can trigger ten or more signal transduction
pathways at once
• Abnormal tyrosine kinases that work even without
a signal molecule may contribute to some cancers
Signal
molecule
Signal-binding site
a Helix in the
membrane
Signal
molecule
Tyrosines
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Receptor tyrosine
kinase proteins
(inactive monomers)
CYTOPLASM
Dimer
Activated relay
proteins
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
6
ATP
Activated tyrosinekinase regions
(unphosphorylated
dimer)
6 ADP
P Tyr
P Tyr
P Tyr
Tyr P
Tyr P
Tyr P
Fully activated receptor
tyrosine-kinase
(phosphorylated
dimer)
P Tyr
P Tyr
P Tyr
P
Tyr P
Tyr P
Tyr
Inactive
relay proteins
Cellular
response 1
Cellular
response 2
Ion Channel Receptor
• Acts as a gate when
the receptor changes
shape
• Signal molecule
binds as a ligand to
the receptor, the gate
allows specific ions,
such as Na+ or Ca2+,
through a channel in
the receptor
Receptor
Receptor
Receptor
Receptor
Receptor
Receptor
Transduction
Cascades of molecular interactions relay signals from
receptors to target molecules in the cell
• Transduction usually involves multiple steps
• Multistep pathways can amplify a signal:
A few molecules can produce a large cellular
response
• Multistep pathways provide more opportunities
for coordination and regulation
Signal Transduction
Pathways
The molecules that relay a signal from receptor
to response are mostly proteins
Like falling dominoes, the receptor activates
another protein, which activates another, and so
on, until the protein producing the response is
activated
At each step, the signal is transduced into a
different form, usually a conformational change
Protein Phosphorylation
and Dephosphorylation
In many pathways, the signal is transmitted by a
cascade of protein phosphorylations
Phosphatase enzymes remove the phosphates
This phosphorylation and dephosphorylation
system acts as a molecular switch, turning
activities on and off
Signal molecule
Receptor
Activated relay
molecule
Inactive
protein kinase
1
Active
protein
kinase
1
Inactive
protein kinase
2
ATP
ADP
P
Active
protein
kinase
2
PP
Pi
Inactive
protein kinase
3
ATP
ADP
Pi
Active
protein
kinase
3
PP
Inactive
protein
P
ATP
P
ADP
Pi
PP
Active
protein
Cellular
response
Small Molecules and Ions as
Second Messengers
Second messengers are small, nonprotein, watersoluble molecules or ions
The extracellular signal molecule that binds to the
membrane is a pathway’s “first messenger”
Second messengers can readily spread throughout
cells by diffusion
Second messengers participate in pathways
initiated by G-protein-linked receptors and
receptor tyrosine kinases
Cyclic AMP
 Cyclic AMP (cAMP) is one of the most widely used second
messengers
 Adenylyl cyclase, an enzyme in the plasma membrane, converts
ATP to cAMP in response to an extracellular signal
 Many signal molecules trigger formation of cAMP
 Other components of cAMP pathways are G proteins, G-proteinlinked receptors, and 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
Phosphodiesterase
Adenylyl cyclase
Pyrophosphate
P
ATP
H2O
Pi
Cyclic AMP
AMP
First messenger
(signal molecule
such as epinephrine)
Adenylyl
cyclase
G protein
G-protein-linked
receptor
GTP
ATP
cAMP
Second
messenger
Protein
kinase A
Cellular responses
Calcium ions and 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
 A signal relayed by a signal transduction pathway may
trigger an increase in calcium in the cytosol
 Pathways leading to the release of calcium involve inositol
triphosphate (IP3) and diacylglycerol (DAG) as second
messengers
EXTRACELLULAR Signal molecule
FLUID
(first messenger)
G protein
DAG
GTP
G-protein-linked
receptor
IP3-gated
calcium channel
Endoplasmic
reticulum (ER)
CYTOSOL
Ca2+
Phospholipase C
PIP2
IP3 (second
messenger)
EXTRACELLULAR Signal molecule
FLUID
(first messenger)
G protein
DAG
GTP
G-protein-linked
receptor
Phospholipase C
IP3 (second
messenger)
IP3-gated
calcium channel
Endoplasmic
reticulum (ER)
CYTOSOL
PIP2
Ca2+
Ca2+
(second
messenger)
EXTRACELLULAR Signal molecule
FLUID
(first messenger)
G protein
DAG
GTP
G-protein-linked
receptor
Phospholipase C
PIP2
IP3 (second
messenger)
IP3-gated
calcium channel
Endoplasmic
reticulum (ER)
CYTOSOL
Ca2+
Ca2+
(second
messenger)
Various
proteins
activated
Cellular
responses
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