Chapter 11~Chapter 11~Cell Cell

CommunicationCommunication

Signal-transduction Signal-transduction pathway Ipathway I DefDef: Process by which a signal on a cell’s surface : Process by which a signal on a cell’s surface

is converted into a specific cellular responseis converted into a specific cellular response Local signaling Local signaling (short distance): (short distance):

• Messenger moleucles are secreted and travel short Messenger moleucles are secreted and travel short distancesdistances

• Paracrine signaling (growth factors)Paracrine signaling (growth factors)– Single cell produces factors that are received and responded to Single cell produces factors that are received and responded to

by numerous cells simultaneouslyby numerous cells simultaneously

• Synaptic (neurotransmitters)Synaptic (neurotransmitters)– Electrical signal stimlates secretion of chem signal which Electrical signal stimlates secretion of chem signal which

moves across the synapse to another cellmoves across the synapse to another cell

Signal-transduction Signal-transduction pathway IIpathway II Long distanceLong distance: hormones: hormones

• Animals - aka endocrine signalingAnimals - aka endocrine signaling– Hormones released into circulatory system to Hormones released into circulatory system to

travel to target cellstravel to target cells– Nervous system – signal continues along a Nervous system – signal continues along a

series of cellsseries of cells• Plants – growth regulatorsPlants – growth regulators

– Travel by vessels, diffusion through cells, or Travel by vessels, diffusion through cells, or the air as a gasthe air as a gas

Stages of cell signalingStages of cell signaling Discovered by Earl Sutherland (‘71)Discovered by Earl Sutherland (‘71)

• Glycogen depolymerization by epinephrineGlycogen depolymerization by epinephrine 3 steps:3 steps: (1) Reception: target cell detection (1) Reception: target cell detection (2) Transduction: single-step or series of changes(2) Transduction: single-step or series of changes (3) Response: triggering of a specific cellular response(3) Response: triggering of a specific cellular response

Reception IReception I A signal molecule binds to a receptor protein and causes a A signal molecule binds to a receptor protein and causes a

conformation changeconformation change Ligand – molecule that specifically binds to anotherLigand – molecule that specifically binds to another Compare to a key in a lock – similar to enzymes Compare to a key in a lock – similar to enzymes Intracellular receptorsIntracellular receptors

• Proteins found in cytoplasm or nucleus of target cellProteins found in cytoplasm or nucleus of target cell• Messenger must pass through plasma membraneMessenger must pass through plasma membrane• Must be hydrophobic or small enoughMust be hydrophobic or small enough• Ex. Steroids, thyroid hormonesEx. Steroids, thyroid hormones• Testosterone – released by testisTestosterone – released by testis

– Target cells have receptor in nucleusTarget cells have receptor in nucleus– Binds w/ protein activating itBinds w/ protein activating it– Active form enters nucleus and turns on specific genesActive form enters nucleus and turns on specific genes

Reception IIReception II Plasma membrane receptors (pg 206-208)Plasma membrane receptors (pg 206-208)

• Water soluble signal moleculesWater soluble signal molecules• Receptor transmits info by changing shapeReceptor transmits info by changing shape• 3 main types3 main types• (1) G-protein-linked receptors(1) G-protein-linked receptors

– Receptor is made of 7 transmembrane Receptor is made of 7 transmembrane αα helices helices– Works w/ the help of a G protein which is just inside the Works w/ the help of a G protein which is just inside the

membranemembrane– Is on or off depending on which of 2 guanine Is on or off depending on which of 2 guanine

nucleotides is attached (GDP or GTP)nucleotides is attached (GDP or GTP)– Signal molecule binds to receptor and changes its shapeSignal molecule binds to receptor and changes its shape– Binds to GDP causes GTP to replace itBinds to GDP causes GTP to replace it– GTP binds to an enzyme and activates itGTP binds to an enzyme and activates it– Reverts to GDPReverts to GDP

Reception IIIReception III• (2) Receptor Tyrosine Kinases(2) Receptor Tyrosine Kinases

– Can trigger simultaneous signal transduction pathwaysCan trigger simultaneous signal transduction pathways– Regulates cell growth and reproductionRegulates cell growth and reproduction– Malfunction may lead to cancerMalfunction may lead to cancer– Kinase – enzyme catalyzes phosphate transfers in Kinase – enzyme catalyzes phosphate transfers in

cytoplasmcytoplasm– Portion of receptor acts as a tyrosine kinasePortion of receptor acts as a tyrosine kinase– Signal molecule causes 2 receptors to move close Signal molecule causes 2 receptors to move close

together (dimerization)together (dimerization)– Activates tyrosine kinaseActivates tyrosine kinase– Attaches phosphates to tyrosinesAttaches phosphates to tyrosines– Different inactive proteins bind to phosphorylated Different inactive proteins bind to phosphorylated

tyrosine and become activatedtyrosine and become activated

Reception IVReception IV• (3) Ligand-gated ion channels(3) Ligand-gated ion channels

– Important for nervous system Important for nervous system – When receptor changes shape a “gate” When receptor changes shape a “gate”

opens/closes allowing ions through or opens/closes allowing ions through or blocking flowblocking flow

– Cause changes in Na+ and Ca- concentration Cause changes in Na+ and Ca- concentration levelslevels

Transduction ITransduction I Series (cascade) of molecular interactions Series (cascade) of molecular interactions

relay signals from receptors to target relay signals from receptors to target moleculesmolecules

Begins when receptor changesBegins when receptor changes Relay molecules = proteinsRelay molecules = proteins @ each step info is transduced into a @ each step info is transduced into a

different formdifferent form• Usually a conformation change in proteinUsually a conformation change in protein• Caused by phosphorylationCaused by phosphorylation

Transduction IITransduction II• Protein kinase – enzyme that transfers a Protein kinase – enzyme that transfers a

phosphate from ATP to protein – many phosphate from ATP to protein – many different kindsdifferent kinds

• Addition of phosphate activates proteinAddition of phosphate activates protein Dephosphorylation – removal of phosphateDephosphorylation – removal of phosphate

• Inactivates proteins – turn off pathwayInactivates proteins – turn off pathway• Caused by enzymes called protein Caused by enzymes called protein

phosphatasesphosphatases

Second Messengers ISecond Messengers I Small molecules and ions that are not Small molecules and ions that are not

proteinsproteins 11stst is the extracellular signal molecule that is the extracellular signal molecule that

binds to membranebinds to membrane Are able to diffuse through cellsAre able to diffuse through cells 2 most common:cyclic AMP &calcium ions2 most common:cyclic AMP &calcium ions

Second Messengers IISecond Messengers II (1) cyclic AMP (cAMP) (1) cyclic AMP (cAMP)

• Adenylyl cyclase (enzyme Adenylyl cyclase (enzyme in membrane) converts in membrane) converts ATP to cAMPATP to cAMP

• Concen. increases and Concen. increases and spreads through cellspreads through cell

• Only lasts while signal Only lasts while signal molecule is attachedmolecule is attached

• Concen. decreases Concen. decreases because because phosphodiesterase phosphodiesterase changes cAMP back to changes cAMP back to ATPATP

Second Messengers IIISecond Messengers III (2)Calcium ions and Inositol Triphosphate (2)Calcium ions and Inositol Triphosphate

(IP3)(IP3)• Ca concen. increases triggered by other Ca concen. increases triggered by other

secondary messengerssecondary messengers• Phospholipid in membrane is broken into Phospholipid in membrane is broken into

IP3 and diaglycerol (DAG)IP3 and diaglycerol (DAG)• IP3 goes on to stimulate Ca increaseIP3 goes on to stimulate Ca increase

ResponseResponse Regulation of cellular activitiesRegulation of cellular activities In cytoplasmIn cytoplasm Ex. Open/close ion channel; change in Ex. Open/close ion channel; change in

metabolismmetabolism May cause synthesis of enzymesMay cause synthesis of enzymes

Specificity of Cell SignalingSpecificity of Cell Signaling Get different results from different Get different results from different

cells because they have different cells because they have different collections of proteinscollections of proteins

Ex. Epinephrine – a liver cell breaks Ex. Epinephrine – a liver cell breaks down glycogen; heart cells contract for down glycogen; heart cells contract for faster heart beatfaster heart beat

Signaling EfficiencySignaling Efficiency Scaffolding proteins – large relay Scaffolding proteins – large relay

proteins w/ other relay proteins proteins w/ other relay proteins attachedattached

Increases efficiency Increases efficiency