Signal transduction pathways in rheumatoid arthritis with emphasis ...
Signal Transduction Pathways “ From signal to gene expression ”
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Transcript of Signal Transduction Pathways “ From signal to gene expression ”
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
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
Overview on Plant Signal Transduction
Analogy view of cell signaling transduction pathway
Input (command)Keyboard
Signalperception
Endogenous:phytohormoneExogenous:environmental cue
CPU (Central
Processing Unit)ChipSignal
Transduction NetworkCompiling, Integration,processing
Output (performance
)PrinterSignal
ResponseMorphogenesis change,Growth development differentiation
EXTRACELLULARFLUID
Reception
Plasma membrane
Transduction CYTOPLASM
Receptor
Signalmolecule
EXTRACELLULARFLUID
Reception
Plasma membrane
Transduction CYTOPLASM
Receptor
Signalmolecule
Relay molecules in a signal transductionpathway
EXTRACELLULARFLUID
Reception
Plasma membraneTransduction CYTOPLASM
Receptor
Signalmolecule
Relay molecules in a signal transductionpathway
Response
Activationof cellularresponse
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
Overview on Plant Signal Transduction
STIMULUS
R
R
Ca2+
Ca2+
G-prot
Kin
Phos
TF
Plasmamembrane
Nuclear membrane
DNA
Signal transduction (Simplified model)
Stimulus Hormones, physical environment, pathogensReceptor On the plasmamembrane, or internalSecondary messengers Ca2+, G-proteins, Inositol PhosphateEffector molecules Protein kinases or phosphatases Transcription factorsResponse Stomatal closure Change in growth direction
Signal Transduction Components
How many signal factors whichPlant will respond to? --biotic and abiotic factors--
STIMULUS
Stimulus
Reception
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
A signal molecule binds to a receptor protein, causing it to change shape
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 receptors2. Receptor tyrosine kinases3. Ion channel receptors
• 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
G-protein-linked Receptor
Segment thatinteracts withG proteins
Signal-binding site
G-protein-linked receptor
• 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
Receptor Tyrosine Kinases
Signalmolecule
Helix in themembrane
Signal-binding site
Tyr
Tyr
Tyr Tyr
Tyr
TyrTyrosines
Receptor tyrosinekinase proteins(inactive monomers)CYTOPLASM
Tyr
Tyr
Tyr Tyr
Tyr
Tyr Tyr
Tyr
Tyr Tyr
Tyr
Tyr
Tyr
Tyr
Tyr Tyr
Tyr
Tyr
Activated tyrosine-kinase regions(unphosphorylateddimer)
Signalmolecule
Dimer
Fully activated receptor tyrosine-kinase(phosphorylateddimer)
Tyr
Tyr
Tyr Tyr
Tyr
TyrPPP
PPPATP 6 ADP
Tyr
Tyr
Tyr Tyr
Tyr
TyrP
PP
PPP
Inactiverelay proteins
Cellularresponse 2
Cellularresponse 1
Activated relay proteins
6
• 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
Ion Channel Receptor
Receptor
Receptor
Receptor
Receptor
Receptor
Receptor
Transduction
• 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
Cascades of molecular interactions relay signals from receptors to target molecules in
the cell
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
Activated relaymolecule
Receptor
Inactiveprotein kinase
1 Activeprotein kinase
1
Inactiveprotein kinase
2 Activeprotein kinase
2
Inactiveprotein kinase
3 Activeprotein kinase
3
ADP
Inactiveprotein
Activeprotein
Cellularresponse
Phosphorylation cascade
ATP
PPP i
ADPATP
PPP i
ADPATP
PPP i
P
P
P
Small Molecules and Ions as Second Messengers
Second messengers are small, nonprotein, water-soluble 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-protein-linked 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
ATP Cyclic AMP AMP
Adenylyl cyclase
PyrophosphateP P i
Phosphodiesterase
H2O
cAMP
ATPSecondmessenger
First messenger(signal moleculesuch as epinephrine)
G-protein-linkedreceptor
G protein
Adenylylcyclase
Proteinkinase A
Cellular responses
GTP
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
CYTOSOL
Ca2+Endoplasmicreticulum (ER)
IP3-gatedcalcium channel
IP3 (secondmessenger)
DAG
PIP2G-protein-linkedreceptor Phospholipase C
G protein
Signal molecule(first messenger)
EXTRACELLULARFLUID
GTP
CYTOSOL
Ca2+Endoplasmicreticulum (ER)
IP3-gatedcalcium channel
IP3 (secondmessenger)
DAG
PIP2G-protein-linkedreceptor Phospholipase C
G protein
Signal molecule(first messenger)
EXTRACELLULARFLUID
GTP
Ca2+ (secondmessenger)
CYTOSOL
Ca2+Endoplasmicreticulum (ER)
IP3-gatedcalcium channel
IP3 (secondmessenger)
DAG
PIP2G-protein-linkedreceptor Phospholipase C
G protein
Signal molecule(first messenger)
EXTRACELLULARFLUID
GTP
Ca2+ (secondmessenger)
Variousproteinsactivated
Cellularre-sponses