BCMB 230 1st Edition Lecture 7 Outline of Last Lecture I.DiffusionII.Different Types of DiffusionIII.Exocytosis and EndocytosisIV.OsmosisV.TonicityOutline of Current Lecture I.MessengersII.Pathways through Second MessengersIII.G Protein Coupled ReceptorsCurrent LectureSignal TransductionSignal transduction-the mechanism for generating a cellular response when a cell receives a stimulus/signal/chemical messenger-divide chemical messengers into two groups: lipid soluble and water soluble-receptors for these pathways are in different locations:-receptors for lipid soluble messengers are inside the cell-receptors for water soluble messengers are in the plasma membrane of the cellI. MessengersLipid soluble messenger-generally act on cells by binding to intracellular (inactive) receptor proteins; most inactive receptors already reside in the cell nucleus where they bind to and are activated by their respective ligands; the lipid soluble messenger moves through cell membrane since it is permeable to it and goes into the nucleus to interact with nuclear proteins that have binding site for it and initiates DNA transcription to mRNA; translation of mRNA produces a new protein that causes the cell to change/respond to stimuli (increases cellular concentration of the protein and/or its rate of secretion-in some cases, transcription can be decrease by the activated receptorWater soluble messenger-have to interact with a membrane protein (receptor) in order to causea response within the cell because the messenger is going to be stuck outside of the cell;uses first and second messengersThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.-First messenger-intercellular chemical messengers that reach the cell and bind to their specific plasma membrane receptors-Second messenger-substances that enter or are generated in the cytoplasm as a result of receptor activation by the first messenger; can move (diffuse) throughout the cell to activate proteins that are away from the membrane-can go to nucleus and initiate transcription-can go to ER and start translation-can go to other places within the cell -multi-step processes are more easily regulated than single step responses, allow for deeper activation of proteins and can amplify signal/stimulus (work more than once); secondarymessenger allows you to move away from membrane (not restricted)II. Pathways through Second MessengersPathways using second messengers will only be ones with a water soluble messenger.-Term to know: Protein kinase-name for any enzyme that phosphorylates other proteins by transferring a phosphate group to them from ATP and changes protein activity-pathways may involve a series of reactions in which a particular inactive protein kinase is activated by phosphorylation and then catalyzes the phosphorylation of another inactive protein kinase, and so on… -at the ends of these sequences, the ultimate phosphorylation of key proteins (transporters, metabolic enzymes, ion channels, contractile proteins) underlies the cell’s biochemical response to the first messenger-ligand gated ion channel-protein has a binding site and an ion channel; first messenger--ligand (chemical messenger)—binds to the binding site, resulting in a change of the receptor toopen the channel (which changes membrane potential), allowing material through; results in the increase in the net diffusion across the plasma membrane of one or more types of ions specific to that channel-tyrosine kinase-an enzyme that constitutes a great majority of enzyme receptors that specifically phosphorylate the portions of proteins that contain the amino acid tyrosine-receptor protein (transmembrane) has a binding site on outside of cell, messenger binds and changes the shape of the receptor so that its enzymatic portion, located on the cytoplasmic side of the plasma membrane, is activated -results in the autophosphorylation of the receptor—receptor phosphorylates its own tyrosine groups -cause tyrosine kinase activity inside cell, causes protein phosphorylation (activation of proteins) inside cell basically covalent modulation (turns protein on or off) -JAK kinase-the enzymatic activity is not in the receptor but in a janus kinase (JAK); kinase is a separate protein but still associated with the receptor—the receptor and its associated janus kinase fuction as a unit-binding of first messenger to the receptor causes a change in receptor that leads to activation of the janus kinase which results in new proteins -same process as tyrosine kinaseIII. G Protein Coupled Receptors*also part of the second messenger pathways*Term to know: G protein-has three different membrane proteins: -receptor -G protein-associated with receptor in the membrane; becomes activated by splitting, which activates protein)-effector protein (ion channel, transporter, or enzyme) -G Protein is a protein complex located on the cytosolic surface of the plasma membrane, bound to the inactive receptor -First messenger binds to receptor changing its shape; activated receptor makes a part ofthe G protein to link up with another plasma membrane protein (an ion channel or an enzyme) -G protein couples a receptor to an ion channel or to an enzyme in the plasma membrane—may cause an ion channel to open or activate or inhibit the membrane enzyme it interacts with; such enzymes when activated, cause the generation of second messengers inside the cell-Two most important effector protein enzymes regulated by g proteins: adenylyl cyclase and phospholipase C-cyclic AMP (adenylyl cyclase)-First messenger binds to receptor which activates its associated g protein; then the g protein activates its effector protein, a membrane enzyme called adenylyl cyclase- When adenylyl cyclase is activated, whose catalytic site is located on the inside of the cell of the plasma membrane, it catalyzes the conversion of cytosolic ATP molecules to cyclic AMP (cAMP)—not a reversible reaction (takes off high energy groups)-cAMP acts as a secondary messenger-diffuses throughout the cell to trigger the sequence of events: cAMP binds to and activates an enzyme called cAMP-dependent protein that phosphorylates a protein-can break down cAMP by using phophodiesterase-activation of adenylyl cyclase by a G protein initiates an “amplification cascade” of events that converts proteins in sequence from inactive to active forms—a