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 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

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

EXTRACELLULAR FLUID Reception Transduction CYTOPLASM Plasma membrane Receptor Signal molecule

Relay molecules in a signal transduction EXTRACELLULAR FLUID CYTOPLASM Reception Transduction Plasma membrane Receptor Relay molecules in a signal transduction pathway Signal molecule

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

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

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

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

G-protein-linked receptor 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

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

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 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

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

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

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

Pyrophosphate ATP Cyclic AMP AMP Phosphodiesterase Adenylyl cyclase

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

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 PIP2 Phospholipase C IP3 (second messenger) IP3-gated calcium channel Endoplasmic reticulum (ER) Ca2+ CYTOSOL

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

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

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。