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Transcript
Cell Communication AP Biology Minzenmayer Cell Signaling 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 Signal transduction pathways convert signals on a cell’s surface into cellular responses AP Biology Minzenmayer Signaling with Direct Contact AP Biology Minzenmayer Local vs. Long Distance Signaling Animal cells communicate using local regulators messenger molecules—travel short distances Growth factors long-distance signaling Hormones Gases traveling through air in plants AP Biology Minzenmayer Local Signaling w/o Direct Contact Interferon released from viral infected cells Growth factors Paracrine Signaling AP Biology Synaptic Signaling Minzenmayer Long-Distance Signaling AP Biology Hormone Signaling Minzenmayer Long-Distance Diffusion Note how specificity is determined by presence/absence of receptor protein AP Biology Minzenmayer Signaling, Free-Living Cells AP Biology factor Receptor 1 Exchange of mating factors a a factor Yeast cell, Yeast cell, mating type a mating type 2 Mating 3 New a/ cell a a/ Minzenmayer Cell-Cell Chemical Signaling Involves physical movement of ligands Small molecule that specifically binds to larger molecule Ligand reception by proteins Protein usually has change in conformation after binding AP Biology Minzenmayer Fig. 11-6-1 Signal Transduction EXTRACELLULAR FLUID 1 Reception Receptor Signaling molecule CYTOPLASM Plasma membrane Fig. 11-6-2 Signal Transduction CYTOPLASM EXTRACELLULAR FLUID Plasma membrane 1 Reception 2 Transduction Receptor Relay molecules in a signal transduction pathway Signaling molecule Fig. 11-6-3 Signal Transduction CYTOPLASM EXTRACELLULAR FLUID Plasma membrane 1 Reception 2 Transduction 3 Response Receptor Activation of cellular response Relay molecules in a signal transduction pathway Signaling molecule Signal Transduction AP Biology Minzenmayer Receptors in Plasma Membrane Most water-soluble Three main types: G protein-coupled receptors Receptor tyrosine kinases Ion channel receptors AP Biology Minzenmayer G Proteins G protein-coupled receptor plasma membrane receptor that works with the help of a G protein G protein acts as an on/off switch: If GDP is bound to the G protein, G protein is inactive AP Biology Minzenmayer AP Biology Minzenmayer Fig. 11-7b G-Protein-Linked Receptor G protein-coupled receptor Plasma membrane 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 Tyrosine Kinases Receptor tyrosine kinases membrane receptors that attach phosphates to tyrosines can trigger multiple signal transduction pathways at once AP Biology Minzenmayer Protein Kinase & Phosphatase O Protein Kinase OH + ATP Protein Protein O P O + ADP O Pi H2O Protein Phosphatase AP Biology Minzenmayer AP Biology Response Transduction Phosphorylization Receptor dimerization Ligand Reception Tyrosine Kinase Receptor Minzenmayer Ligand Gated Ion Channel ligand-gated ion channel receptor acts as gate when receptor changes shape When signal molecule binds as a ligand to receptor, gate allows specific ions, such as Na+ or Ca2+, through a channel in receptor AP Biology Minzenmayer Ion-Channel Receptor AP Biology Reversibility is assured by pumping ions back out again (using separate protein) Minzenmayer Intracellular Receptors Some receptor proteins are intracellular found in cytosol or nucleus of target cells Small or hydrophobic chemical messengers can readily cross membrane and activate receptors Examples of hydrophobic messengers steroid and thyroid hormones of animals An activated hormone-receptor complex can act as a transcription factor turning on specific genes AP Biology Minzenmayer Fig. 11-8-1 Intracellular Receptor Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein DNA NUCLEUS CYTOPLASM Fig. 11-8-2 Intracellular Receptor Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormonereceptor complex DNA NUCLEUS CYTOPLASM Fig. 11-8-3 Intracellular Receptor Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormonereceptor complex DNA NUCLEUS CYTOPLASM Fig. 11-8-4 Intracellular Receptor Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormonereceptor complex DNA mRNA NUCLEUS CYTOPLASM Fig. 11-8-5 Intracellular Receptor Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormonereceptor complex DNA mRNA NUCLEUS CYTOPLASM New protein AP Biology Minzenmayer Intracellular Receptor Transduction molecules that relay a signal from receptor to response are mostly proteins reception activates another protein, which activates another, …..until protein producing response is activated At each step, signal is transduced into a different form, usually a shape change in a protein AP Biology Minzenmayer Protein Phosphorylation & Dephosphorylation In many pathways, signal is transmitted by cascade of protein phosphorylations Protein kinases transfer phosphates from ATP to protein, a process called phosphorylation Protein phosphatases remove phosphates from proteins, a process called dephosphorylation phosphorylation and dephosphorylation system acts as molecular switch, turning activities on and off AP Biology Minzenmayer Phosphorylation Cascade Signaling molecule Receptor Activated relay molecule Inactive protein kinase 1 Activates protein kinase Active protein kinase 1 Inactive protein kinase 2 Active PK1 transfers P From ATP to inactive PK2 ATP Active protein kinase 2 ADP Pi PP Inactive ATP protein kinase 3 Protein phosphatases (PP) catalyze removal of P to make them inactive again P ADP Pi Active protein kinase 3 PP Inactive protein P ATP P ADP Pi PP Active protein Cellular response Small Molecules & Ions Second Messengers first messenger extracellular signal molecule that binds to receptor Second messengers small, non-protein, water-soluble molecules or ions that spread throughout a cell by diffusion participate in pathways initiated by G protein-coupled receptors and receptor tyrosine kinases Cyclic AMP and calcium ions are common second messengers AP Biology Minzenmayer Cyclic AMP cAMP widely used second messengers Adenylyl cyclase enzyme in plasma membrane converts ATP to cAMP in response to extracellular signal AP Biology Minzenmayer Cyclic AMP (cAMP) Note reversibility “Second” Messenger AP Biology Second messengers are not proteins Minzenmayer cAMP Many signal molecules trigger formation of cAMP Other components of cAMP pathways are G proteins G protein-coupled receptors 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 AP Biology Minzenmayer cAMP as a 2nd Messenger Fig. 11-11 First messenger Adenylyl cyclase G protein G protein-coupled receptor GTP ATP cAMP Second messenger Protein kinase A Cellular responses Cell Signaling - Disease Cholera Caused by Vibrio cholerae in contaminated water Toxin secreted by V. cholerae in small intestine Toxin modifies G protein involved in salt/water secretion Can no longer hydrolyze GTP Always active - stimulates cAMP production Intestinal cells secrete water/ions Severe diarrhea often lethal due to dehydration and salt imbalance Cell Signaling - Cholera Intestinal Lumen H2O, ions Ext Int GTP active Intestinal Cell GDP Toxin inactive cAMP Copyright © 2005 Pearson Education, Inc., publishing as Benjamin Cummings H2O, ions Net Effect Calcium Ions & 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 AP Biology Minzenmayer Fig. 11-12 EXTRACELLULAR FLUID Active transport of Ca2+ ions out of cell Active transport into lumen of ER and mitochondrion Plasma membrane Ca2+ pump ATP Mitochondrion Nucleus CYTOSOL Ca2+ pump Endoplasmic reticulum (ER) Signal transduction results in release of Ca from ER ATP Key High [Ca2+] Low [Ca2+] Ca2+ pump Calcium Ions & Inositol Triphosphate (IP3) Signal relayed by signal transduction pathway may trigger increase in calcium in the cytosol Pathways leading to release of calcium involve inositol triphosphate (IP3) and diacylglycerol (DAG) as additional second messengers AP Biology Minzenmayer Ca2+-mediated Signal Amp. Fig. 11-13-1 EXTRACELLULAR FLUID Signaling molecule (first messenger) G protein DAG GTP G protein-coupled receptor Phospholipase C PIP2 IP3 (second messenger) IP3-gated calcium channel Endoplasmic reticulum (ER) CYTOSOL Ca2+ Fig. 11-13-2 EXTRACELLULAR FLUID Signaling molecule (first messenger) G protein DAG GTP G protein-coupled receptor Phospholipase C PIP2 IP3 (second messenger) IP3-gated calcium channel Endoplasmic reticulum (ER) CYTOSOL Ca2+ Ca2+ (second messenger) Fig. 11-13-3 EXTRACELLULAR FLUID Signaling molecule (first messenger) G protein DAG GTP G protein-coupled receptor PIP2 Phospholipase C IP3 (second messenger) IP3-gated calcium channel Endoplasmic reticulum (ER) CYTOSOL Various proteins activated Ca2+ Ca2+ (second messenger) Cellular responses Ca2+-mediated Signal Amp. AP Biology Releasing Ca2+ is a means of greatly amplifying signal Minzenmayer Response Cell signaling leads to regulation of transcription activities or cytoplasmic activities cell’s response to extracellular signal sometimes called “output response” AP Biology Minzenmayer Nuclear & Cytoplasmic Responses signal transduction pathway leads to regulation of one or more cellular activities response may occur in cytoplasm or may involve action in nucleus Many signaling pathways regulate synthesis of proteins usually by turning genes on or off in nucleus final activated molecule may function as transcription factor AP Biology Minzenmayer Fig. 11-14 Growth factor Reception Nuclear Response Receptor Phosphorylation cascade Transduction CYTOPLASM Inactive transcription factor Active transcription factor P Response DNA Gene NUCLEUS mRNA Signaling pathways can affect physical characteristics of a cell--cell shape RESULTS ∆Fus3 Wild-type (shmoos) ∆formin CONCLUSION 1 Mating factor G protein-coupled receptor Shmoo projection forming Formin P Fus3 GTP GDP Phosphorylation cascade 2 Actin subunit P Formin Formin P 4 Fus3 Fus3 P Microfilament 5 3 Fine Tuning Response Multistep pathways have two important benefits: Amplifying signal and therefore the response Contributing to specificity of response Signal Amplification Enzyme cascades amplify cell’s response At each step, number of activated products is much greater than in preceding step AP Biology Minzenmayer Signal Amplification (Cascade) AP Biology Minzenmayer Signal Amplification (Cascade) AP Biology Minzenmayer Signal-Transduction Cascade Fig. 11-15 Reception Binding of epinephrine to G protein-coupled receptor (1 molecule) Transduction Inactive G protein Active G protein (102 molecules) Inactive adenylyl cyclase Active adenylyl cyclase (102) ATP Cyclic AMP (104) Inactive protein kinase A Active protein kinase A (104) Inactive phosphorylase kinase Active phosphorylase kinase (105) Inactive glycogen phosphorylase Active glycogen phosphorylase (106) Response Glycogen Glucose-1-phosphate (108 molecules) Specificity & Coordination of Response Different kinds of cells have different collections of proteins allow cells to detect & respond to different signals Even same signals can have different effects in cells with different proteins and pathways Pathway branching and “cross-talk” further help cell coordinate incoming signals AP Biology Minzenmayer Fig. 11-17a Signaling molecule Receptor Relay molecules Response 1 Cell A. Pathway leads to a single response. Response 2 Response 3 Cell B. Pathway branches, leading to two responses. Fig. 11-17b Activation or inhibition Response 4 Cell C. Cross-talk occurs between two pathways. Response 5 Cell D. Different receptor leads to a different response. Signaling Efficiency Scaffolding proteins large relay proteins to which other relay proteins are attached can increase signal transduction efficiency Groups together different proteins involved in same pathway AP Biology Minzenmayer Fig. 11-18 Signaling molecule Plasma membrane Receptor Three different protein kinases Scaffolding protein Termination of Signal Inactivation mechanisms are an essential aspect of cell signaling When signal molecules leave receptor it reverts to inactive state AP Biology Minzenmayer Apoptosis Programmed or controlled cell suicide integrates multiple cell-signaling pathways Cell chopped & packaged into vesicles that are digested by scavenger cells prevents enzymes from leaking out of dying cell and damaging neighboring cells Caspases main proteases that carry out apoptosis can be triggered by: AP Biology An extracellular death-signaling ligand DNA damage in the nucleus Protein misfolding in the endoplasmic reticulum Minzenmayer Fig. 11-20a Ced-9 protein (active) inhibits Ced-4 activity Mitochondrion Receptor for deathsignaling molecule Ced-4 Ced-3 Inactive proteins (a) No death signal Fig. 11-20b Ced-9 (inactive) Cell forms blebs Deathsignaling molecule Active Active Ced-4 Ced-3 Activation cascade (b) Death signal Other proteases Nucleases AP Biology Minzenmayer Fig. 11-21 Interdigital tissue 1 mm Fig. 11-UN1 1 Reception 2 Transduction 3 Response Receptor Relay molecules Signaling molecule Activation of cellular response AP Biology Minzenmayer AP Biology Minzenmayer AP Biology Minzenmayer