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Transcript
Regulation - cells need to control cellular processes. Environmental Stimuli - cells need to be able to respond to signals from their environment. A signal transduction pathway is a series of steps by which a signal on a cell’s surface is converted into a specific cellular response Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Fig. 11-2 factor Receptor 1 Exchange of mating factors a a factor Yeast cell, mating type a 2 Mating 3 New a/ cell Yeast cell, mating type a a/ Pathway similarities suggest that ancestral signaling molecules evolved in prokaryotes and were modified later in eukaryotes Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings In many cases, animal cells communicate using local regulators, messenger molecules that travel only short distances In long-distance signaling, plants and animals use chemicals called hormones Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings 1. Reception - receiving the signal. 2. Transduction - passing on the signal. 3. Response - cellular changes because of the signal. The target cell’s detection of a signal coming from outside the cell. May occur by: Direct Contact Through signal molecules When molecules can flow directly from cell to cell without crossing membranes. Plants - plasmodesmata Animals - gap junctions May also occur by cell surface molecules that project from the surface and “touch” another cell. The actual chemical signal that travels from cell to cell. Often water soluble. Usually too large to travel through membranes. Double reason why they can’t cross cell membranes. Behave as “ligands”: a smaller molecule that binds to a larger one. Usually made of protein. Change shape when bind to a signal molecule. Transmits information from the exterior to the interior of a cell. 1. G-Protein linked 2. Tyrosine-Kinase 3. Ion channels 4. Intracellular Plasma membrane receptor. Works with “G-protein”, an intracellular protein with GDP or GTP. GDP and GTP acts as a switch. If GDP - inactive If GTP - active When active (GTP), the protein binds to another protein (enzyme) and alters its activation. Active state is only temporary. Fig. 11-7b Plasma membrane G protein-coupled receptor Activated receptor Inactive enzyme Signaling molecule GDP CYTOPLASM GDP Enzyme G protein (inactive) GTP 2 1 Activated enzyme GTP GDP Pi Cellular response 3 4 Very widespread and diverse in functions. Ex - vision, smell, blood vessel development. Many diseases work by affecting g-protein linked receptors. Ex - whooping cough, botulism, cholera, some cancers Up to 60% of all medicines exert their effects through G-protein linked receptors. Extends through the cell membrane. Intracellular part functions as a “kinase”, which transfers P from ATP to tyrosine on a substrate protein. 1. Ligand binding - causes two receptor molecules to aggregate. 2. Activation of Tyrosine-kinase parts in cytoplasm. 3. Phosphorylation of tyrosines by ATP. 4. After phophorylation, receptor protein fully activated and is recognized by specific relay proteins in cell Fig. 11-7c Ligand-binding site Signaling molecule (ligand) Signaling molecule Helix Tyrosines Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Receptor tyrosine kinase proteins CYTOPLAS M Dimer 1 2 Activated relay proteins Tyr Tyr Tyr Tyr Tyr Tyr P Tyr P Tyr 6 ATP Activated tyrosine kinase regions 6 ADP P Tyr Tyr P Tyr Tyr Tyr P Tyr P Tyr Tyr P P Tyr P P P Tyr P Fully activated receptor tyrosine kinase Inactive relay proteins 3 4 Cellular response 1 Cellular response 2 Often activate several different pathways at once, helping regulate complicated functions such as cell division. Protein pores in the membrane that open or close in response to chemical signals. Allow or block the flow of ions such as Na+ or Ca2+. Activated by a ligand on the extracellular side. Causes a change in ion concentration inside the cell. Ex - nervous system signals. Become activated & cause the cellular response. Proteins located in the cytoplasm or nucleus that receive a signal that CAN pass through the cell membrane. Ex - steroids (hormones), NO - nitric oxide Activated protein turns on genes in nucleus. Fig. 11-8-1 Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein DNA NUCLEUS CYTOPLASM Fig. 11-8-2 Hormone (testosterone) EXTRACELLULA R FLUID Plasma membrane Receptor protein Hormonereceptor complex DNA NUCLEUS CYTOPLASM Fig. 11-8-3 Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormonereceptor complex DNA NUCLEUS CYTOPLASM Fig. 11-8-4 Hormone (testosterone) EXTRACELLULA R FLUID Plasma membrane Receptor protein Hormonereceptor complex DNA mRNA NUCLEUS CYTOPLASM Fig. 11-8-5 Hormone (testosterone) Video clip http://highered.mc grawhill.com/sites/0072 507470/student_vi ew0/chapter17/ani mation__intracellu lar_receptor_mode l.html EXTRACELLULA R FLUID Plasma membrane Receptor protein Hormonereceptor complex DNA mRNA NUCLEUS CYTOPLAS M New protein Often has multiple steps using relay proteins such as Protein Kinases Question #9: amplification of signal provide more opportunities for coordination and regulation of the cellular response Protein kinases transfer phosphates from ATP to protein… phosphorylation (this activates the protein) Protein phosphatases remove the phosphates from proteins… dephosphorylation Acts as a molecular switch Fig. 11-9 Signaling molecule Receptor Activated relay molecule Inactive protein kinase 1 Active protein kinase 1 Inactive protein kinase 2 ATP ADP Pi P Active protein kinase 2 PP Inactive protein kinase 3 ATP ADP Pi Active protein kinase 3 PP Inactive protein P ATP P ADP Pi PP Active protein Cellular response Protein Kinases often work in a cascade with each being able to activate several molecules. Result - from one signal, many molecules can be activated. Small water soluble, non-protein molecules or ions that pass on a signal. Spread rapidly by diffusion. Activates relay proteins. Examples - cAMP, Ca2+ A form of AMP made directly from ATP by Adenylyl cyclase (enzyme) Short lived - converted back to AMP (by Phosphodiesterase) Activates a number of Protein Kinases which then phosphorylates various other proteins Fig. 11-11 First messenger Adenylyl cyclase G protein G protein-coupled receptor GTP ATP cAMP http://highered.mcgrawhill.com/sites/0072507470/student_ view0/chapter17/animation__secon d_messenger__camp.html Second messenger Protein kinase A Cellular responses More widely used than cAMP. Used as a secondary messenger in both Gprotein pathways and tyrosine-kinase receptor pathways. Works because of differences in concentration between extracellular and intracellular environments. (10,000X) Involved in muscle cell contraction and cell division Fig. 11-12 EXTRACELLULA R FLUID Plasma membrane Ca2+ pump ATP Mitochondrion Nucleus CYTOSOL Ca2+ pump Endoplasmic reticulum (ER) ATP Key High [Ca2+] Low [Ca2+] Ca2+ pump Secondary messenger attached to phospholipids of cell membrane. Sent to Ca channel on the ER. Allows flood of Ca2+ into the cytoplasm from the ER, which activate the next protein in one or more signaling pathways (video animation from Campbell)11_13SignalTransduction_A.swf Start here Or Start here #18 Cytoplasmic Regulation Transcription Regulation in the nucleus (DNA --> RNA). Rearrangement of the cytoskeleton. Opening or closing of an ion channel. Alteration of cell metabolism. Activating protein synthesis for new enzymes. Transcription control factors are often activated by a Protein Kinase. Enzyme cascades amplify the cell’s response At each step, the number of activated products is much greater than in the preceding step http://highered.mcgrawhill.com/olcweb/cgi/pluginpop.cgi?it=swf::535 ::535::/sites/dl/free/0072437316/120069/bio08 .swf::Signal%20Amplification Different kinds of cells have different collections of proteins (allows cells to detect and respond to different signals) Same signal can have different effects in cells with different proteins and pathways Pathway branching and “cross-talk” further help the cell coordinate incoming signals -Large relay proteins to which other relay proteins are attached -Can increase the signal transduction efficiency by grouping together different proteins involved in the same pathway Fig. 11-18 Signaling molecule Plasma membrane Receptor Three different protein kinases Scaffolding protein Programmed or controlled cell suicide A cell is chopped and packaged into vesicles that are digested by scavenger cells Prevents enzymes from leaking out of a dying cell and damaging neighboring cells Fig. 11-19 2 µm Fig. 11-20 Ced-9 protein (active) inhibits Ced-4 activity Mitochondrion Receptor for deathsignaling molecule Ced-4 Ced-3 Inactive proteins (a) No death signal Ced-9 (inactive) Cell forms blebs Deathsignaling molecule Active Ced-4 Active Ced-3 Activation cascade (b) Death signal Other proteases Nucleases Don’t get bogged down in details in this chapter. Use the KISS principle. Know : 3 stages of cell signaling examples of a receptor and how it works protein kinases and cascades (amplification) example of a secondary messenger