Signal Transduction Pathways

1. Signal Transduction Pathways “From signal to gene expression”

2. 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

3. 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

4. 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

5. EXTRACELLULAR FLUID Transduction CYTOPLASM Reception Plasma membrane Receptor Signal molecule

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

7. EXTRACELLULAR FLUID CYTOPLASM Reception Transduction Response Plasma membrane Receptor Activation of cellular response Relay molecules in a signal transduction pathway Signal molecule

8. 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

10. Signal transduction (Simplified model) STIMULUS Plasma membrane R G-prot Ca2+ Phos Ca2+ Kin Nuclear membrane R TF DNA

11. 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

12. STIMULUS How many signal factors which Plant will respond to? --biotic and abiotic factors--

13. Stimulus

14. 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

15. 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

16. 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

17. 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

18. Signal-binding site Segment that interacts with G proteins G-protein-linked receptor

19. 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

20. Signal molecule Signal-binding site a Helix in the membrane Signal molecule Tyr Tyr Tyrosines 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 P P Tyr Tyr P Tyr Tyr Tyr Tyr P P P Tyr Tyr P Tyr Tyr Tyr Tyr P P P Cellular response 2 Tyr Tyr P Tyr Tyr Tyr P Tyr 6 ATP 6 ADP Activated tyrosine- kinase regions (unphosphorylated dimer) Fully activated receptor tyrosine-kinase (phosphorylated dimer) Inactive relay proteins

21. 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

22. Receptor

23. Receptor

24. Receptor

25. Receptor

26. Receptor

27. Receptor

29. 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

30. 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

31. 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

32. 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 Phosphorylation cascade PP P i Inactive protein kinase 3 ATP ADP P Active protein kinase 3 PP P i Inactive protein ATP P ADP Cellular response Active protein PP P i

33. 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

34. 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

35. Phosphodiesterase Adenylyl cyclase Pyrophosphate H2O P P i ATP Cyclic AMP AMP

36. 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

37. 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

38. EXTRACELLULAR FLUID Signal molecule (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

39. EXTRACELLULAR FLUID Signal molecule (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

40. EXTRACELLULAR FLUID Signal molecule (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