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Signal Transduction Pathways
“From signal to gene expression”
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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
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Overview on Plant Signal Transduction
The stream of signals to which plant cells react is continuous and complex Signal transduction uses a network of interactions within cells, and throughout the plants
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cell signaling transduction pathway
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
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EXTRACELLULAR FLUID Reception Transduction CYTOPLASM Plasma membrane Receptor Signal molecule
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Relay molecules in a signal transduction
EXTRACELLULAR FLUID CYTOPLASM Reception Transduction Plasma membrane Receptor Relay molecules in a signal transduction pathway Signal molecule
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Relay molecules in a signal transduction
EXTRACELLULAR FLUID Reception CYTOPLASM Transduction Response Plasma membrane Receptor Activation of cellular response Relay molecules in a signal transduction pathway Signal molecule
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Overview on Plant Signal Transduction
The stream of signals to which plant cells react is continuous and complex Signal transduction uses a network of interactions within cells, and throughout the plants
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Signal transduction (Simplified model) STIMULUS G-prot R Ca2+ Ca2+ R
Plasma membrane R G-prot Ca2+ Phos Ca2+ Kin Nuclear membrane R TF DNA
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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
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STIMULUS How many signal factors which Plant will respond to?
--biotic and abiotic factors--
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Stimulus
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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
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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
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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
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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
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G-protein-linked receptor
Signal-binding site Segment that interacts with G proteins G-protein-linked receptor
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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
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Fully activated receptor tyrosine-kinase (phosphorylated dimer)
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) Dimer CYTOPLASM Activated relay proteins Cellular response 1 Tyr Tyr P Tyr P Tyr P Tyr Tyr P Tyr Tyr P Tyr Tyr P P P Tyr Tyr Tyr Tyr P Tyr Tyr P P Tyr Tyr P Cellular response 2 6 ATP 6 ADP Activated tyrosine- kinase regions (unphosphorylated dimer) Fully activated receptor tyrosine-kinase (phosphorylated dimer) Inactive relay proteins
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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
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Receptor
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Receptor
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Receptor
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Receptor
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Receptor
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Receptor
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Transduction Transduction usually involves multiple steps
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
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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
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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
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Phosphorylation cascade
Signal molecule Receptor Activated relay molecule Inactive protein kinase 1 Active protein kinase 1 Inactive protein kinase 2 ATP ADP Active protein kinase 2 P Phosphorylation cascade PP P i Inactive protein kinase 3 ATP ADP Active protein kinase 3 P PP P i Inactive protein ATP ADP P Active protein Cellular response PP P i
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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
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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
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Pyrophosphate ATP Cyclic AMP AMP Phosphodiesterase Adenylyl cyclase
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First messenger (signal molecule such as epinephrine) Adenylyl cyclase G protein G-protein-linked receptor GTP ATP Second messenger cAMP Protein kinase A Cellular responses
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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
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EXTRACELLULAR Signal molecule FLUID (first messenger) G protein DAG
GTP G-protein-linked receptor PIP2 Phospholipase C IP3 (second messenger) IP3-gated calcium channel Endoplasmic reticulum (ER) Ca2+ CYTOSOL
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EXTRACELLULAR Signal molecule FLUID (first messenger) G protein DAG
GTP G-protein-linked receptor PIP2 Phospholipase C IP3 (second messenger) IP3-gated calcium channel Endoplasmic reticulum (ER) Ca2+ Ca2+ (second messenger) CYTOSOL
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EXTRACELLULAR Signal molecule FLUID (first messenger) G protein DAG
GTP G-protein-linked receptor PIP2 Phospholipase C IP3 (second messenger) IP3-gated calcium channel Cellular re- sponses Various proteins activated Endoplasmic reticulum (ER) Ca2+ Ca2+ (second messenger) CYTOSOL
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一開始先有訊息認知(signal perception)作用,包括賀爾蒙訊息和接受子(receptor)間辨識,接著靠second messengers 調控細胞內Ca,一般常見second messenger—inositol phosphates 和 ROS。 利用一protein phosphorylation cascade,將原始訊息放大, 最後標的蛋白(target protein)直接參與細胞層級的保護作用或 transcriptional factors所調控的特定逆境調節反應的基因組群。這些基因產物多與調控分子(e,g, ABA, ethylene, and salicylic acid)生成有關。這些分子可以經由不同組成分參與,而開始第二輪的訊息傳導。 訊息傳導需要所有訊息傳導分子間適當的時空協調。因此有些分子參與modification, delivery and assembly of signaling components,而不是直接和訊息接力傳遞有關,但能確定準確的傳送。這些分子包含protein modifer(enzyme for proteim lipidation, methylation,glycosylation, and ubiquitination), sacafold and adaptors。
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