Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings• Which aspects of protein structure change whena protein’s conformation changes?– A. primary.– B. secondary.– C. tertiary.– D. quaternary.– E. both C and DCopyright © 2005 Pearson Education, Inc. publishing as Benjamin CummingsLocal and Long-Distance Signaling• Cells in a multicellular organisms communicate bychemical messengers• Animal and plant cells have cell junctions thatdirectly connect the cytoplasm of adjacent cells• In local signaling, animal cells may communicateby direct contactLE 11-3Plasma membranesGap junctionsbetween animal cellsCell junctionsCell-cell recognitionPlasmodesmatabetween plant cellsCopyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings• In many other cases, animal cells communicateusing local regulators, messenger molecules thattravel only short distances• In long-distance signaling, plants and animals usechemicals called hormonesLE 11-4Paracrine signalingLocal regulatordiffuses throughextracellular fluidSecretoryvesicleSecretingcellTarget cellLocal signalingElectrical signalalong nerve celltriggers release ofneurotransmitterNeurotransmitter diffuses across synapseEndocrine cellBloodvesselLong-distance signalingHormone travelsin bloodstreamto target cellsSynaptic signalingTarget cellis stimulatedHormonal signalingTarget cellCopyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings• Which of the following is true of synapticsignaling and hormone signaling?– A. Hormone signaling occurs in animals only.– B. Hormone signaling is important betweencells that are at greater distances apart thanin synaptic signaling.– C. Both use neurotransmitters, but hormonesignaling is for adjacent cells in animals only.– D. Both are forms of paracrine signaling.Copyright © 2005 Pearson Education, Inc. publishing as Benjamin CummingsThe Three Stages of Cell Signaling: A Preview• Earl W. Sutherland discovered how the hormoneepinephrine acts on cells• Sutherland suggested that cells receiving signalswent through three processes:– Reception– Transduction– ResponseLE 11-5_1EXTRACELLULARFLUIDReceptionPlasma membraneTransductionCYTOPLASMReceptorSignalmoleculeLE 11-5_2EXTRACELLULARFLUIDReceptionPlasma membraneTransductionCYTOPLASMReceptorSignalmoleculeRelay molecules in a signal transductionpathwayLE 11-5_3EXTRACELLULARFLUIDReceptionPlasma membraneTransductionCYTOPLASMReceptorSignalmoleculeRelay molecules in a signal transductionpathwayResponseActivationof cellularresponseCopyright © 2005 Pearson Education, Inc. publishing as Benjamin CummingsConcept 11.2: Reception: A signal molecule bindsto 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 theinitial transduction of the signal• Most signal receptors are plasma membraneproteinsCopyright © 2005 Pearson Education, Inc. publishing as Benjamin CummingsReceptors in the Plasma Membrane• Most water-soluble signal molecules bind tospecific sites on receptor proteins in the plasmamembrane• There are three main types of membranereceptors:– G-protein-linked receptors– Receptor tyrosine kinases– Ion channel receptorsCopyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings• A G-protein-linked receptor is a plasma membranereceptor that works with the help of a G protein• The G-protein acts as an on/off switch: If GDP isbound to the G protein, the G protein is inactiveLE 11-7aaSegment thatinteracts withG proteinsSignal-binding siteG-protein-linked receptorCopyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings• Receptor tyrosine kinases are membranereceptors that attach phosphates to tyrosines• A receptor tyrosine kinase can trigger multiplesignal transduction pathways at onceLE 11-7bSignalmoleculeα Helix in themembraneSignal-binding siteTyrTyrTyr TyrTyrTyrTyrosinesReceptor tyrosinekinase proteins(inactive monomers)CYTOPLASMTyrTyrTyrTyrTyrTyr TyrTyrTyrTyrTyrTyrTyrTyrTyr TyrTyrTyrActivated tyrosine-kinase regions(unphosphorylateddimer)SignalmoleculeDimerFully activated receptor tyrosine-kinase(phosphorylateddimer)TyrTyrTyrTyrTyrTyrPPPPPPATP6 ADPTyrTyrTyr TyrTyrTyrPPPPPPInactiverelay proteinsCellularresponse 2Cellularresponse 1Activated relay proteins6Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings• An ion channel receptor acts as a gate when thereceptor changes shape• When a signal molecule binds as a ligand to thereceptor, the gate allows specific ions, such asNa+ or Ca2+, through a channel in the receptorLE 11-7cSignalmolecule(ligand)GateclosedIonsLigand-gatedion channel receptorPlasmamembraneGate closedGate openCellularresponseCopyright © 2005 Pearson Education, Inc. publishing as Benjamin CummingsSignal Transduction Pathways• The molecules that relay a signal from receptor toresponse are mostly proteins• Like falling dominoes, the receptor activatesanother protein, which activates another, and soon, until the protein producing the response isactivated• At each step, the signal is transduced into adifferent form, usually a conformational changeCopyright © 2005 Pearson Education, Inc. publishing as Benjamin CummingsProtein Phosphorylation and Dephosphorylation• In many pathways, the signal is transmitted by acascade of protein phosphorylations• Phosphatase enzymes remove the phosphates• This phosphorylation and dephosphorylationsystem acts as a molecular switch, turningactivities on and offLE 11-8Signal moleculeActivated relaymoleculeReceptorInactiveprotein kinase1Activeprotein kinase1Inactiveprotein kinase2Activeprotein kinase2Inactiveprotein kinase3Activeprotein kinase3ADPInactiveproteinActiveproteinCellularresponsePhosphorylation cascadeATPPPPiADPATPPPPiADPATPPPPiPPPCopyright © 2005 Pearson Education, Inc. publishing as Benjamin CummingsSmall Molecules and Ions as Second Messengers• Second messengers are small, nonprotein, water-soluble molecules or ions• The extracellular signal molecule that binds to themembrane is a pathway’s “first messenger”• Second messengers can readily spreadthroughout cells by diffusion• Second messengers participate in pathwaysinitiated by G-protein-linked receptors andreceptor tyrosine kinasesCopyright © 2005 Pearson Education, Inc. publishing as Benjamin CummingsCyclic AMP• Cyclic AMP (cAMP) is one of the