1 External signal is received and converted to another form to elicit a response BCOR 011 Lecture 19 Oct 12, 2005 I. Cell Communication – Signal Transduction Chapter 11 2 Lecture Outline Lecture Outline 1. Types of intercellular communication 2. The primary receiver – Receptors 3. - the concept of AMPLIFICATION 4. Types of receptors 5. Ion Channels – Membrane depolarization 6. Trimeric G-Protein coupled receptors - the cAMP signal pathway - the phophatidyl inositol pathway, Ca ++ release 7. Tyrosine Kinase – MAP Kinase Cascade 8. Internal cytosolic receptor systems 3 • Cells sense and respond to the environment Prokaryotes: chemicals Humans: light - rods & cones of the eye sound – hair cells of inner ear chemicals in food – nose & tongue • Cells communicate with each other Direct contact Chemical signals External signals are converted to External signals are converted to Internal Responses Internal Responses
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BCOR 011 Lecture 19 Oct 12, 2005 I. Cell Communication Chapter 11 - uvm.edudstratto/bcor011_handouts/Vayda_lecture_notes/18 … · 1 1 External signal is receivedand converted to
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External signal is received and convertedto another form to elicit a response
BCOR 011 Lecture 19 Oct 12, 2005I. Cell Communication – Signal Transduction
Chapter 11
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Lecture OutlineLecture Outline
1. Types of intercellular communication2. The primary receiver – Receptors
3. - the concept of AMPLIFICATION4. Types of receptors5. Ion Channels – Membrane depolarization6. Trimeric G-Protein coupled receptors
- the cAMP signal pathway- the phophatidyl inositol pathway, Ca++ release
•There are TWO broad subclasses oftrimeric G-protein-activated signal transduction pathways:
depends on their target effector enzymesA. A. adenylyladenylyl cyclasecyclaseB. B. phospholipasephospholipase CC
•All G-proteins – similar structure/activation
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An activated An activated GGαα--proteinprotein--GTPGTP–– Can trigger the formation of Can trigger the formation of cAMPcAMP, , which then acts as a second messenger which then acts as a second messenger in cellular pathwaysin cellular pathways
ATP
GTP
cAMP
Proteinkinase A
Cellular responses
G- protein- linkedreceptor
AdenylylcyclaseG protein
First messenger(signal moleculesuch as epinephrine)
Figure 11.10
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31Like Fig 11-9
GG--proteinprotein--GTP activation ofGTP activation of
Effector Enzyme adenylyladenylyl cyclasecyclaseproduces the 2nd messenger cAMPcAMP
ActivatedG-protein
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cAMPcAMP
activatestarget enzyme
Protein Protein KinaseKinase A (PKAA (PKA)
phosphorylatestarget proteins
InactivePKA
ActiveActivePKAPKA
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inactive
+ P active
PhosphorylasePhosphorylase kinasekinase
Protein Protein KinaseKinase AAPhosphorylates downstream target enzymes
Breaks downStarch
Into Glucose
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34Figure 11.13 Glucose-1-phosphate(108 molecules)
Glycogen
Active glycogen phosphorylase (106)Inactive glycogen phosphorylase
Active phosphorylase kinase (105)Inactive phosphorylase kinase
Inactive protein kinase A
Active protein kinase A (104)
ATP
Cyclic AMP (104)
Active adenylyl cyclase (102)Inactive adenylyl cyclase
Inactive G protein
Active G protein (102 molecules)
Binding of epinephrine to G-protein-linked receptor
IP3 quickly diffuses throughthe cytosol and binds to an IP3–gated calcium channel in the ERmembrane, causing it to open.
4 The calcium ionsactivate the nextprotein in one or moresignaling pathways.
6Calcium ions flow out ofthe ER (down their con-centration gradient), raisingthe Ca2+ level in the cytosol.
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DAG functions asa second messengerin other pathways.
Phospholipase C cleaves aplasma membrane phospholipidcalled PIP2 into DAG and IP3.
A signal molecule bindsto a receptor, leading toactivation of phospholipase C.
EXTRA-CELLULARFLUID
Signal molecule(first messenger)
G protein
G-protein-linkedreceptor
Variousproteinsactivated
Endoplasmicreticulum (ER)
Phospholipase CPIP2
IP3(second messenger)
DAG
Cellularresponse
GTP
Ca2+
(second messenger)
Ca2+
IP3-gatedcalcium channel
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SummarySummary- signaling is endocrine, paracrine, synaptic, or direct cell contact- signal transduction is mediated by receptor proteins- Receptors bind primary signal (ligand)- Some amplification event occurs- Example: ligand gated ion channel opens
influx of ions triggers change in activity (vesicle fusion in nerve end, contraction in muscle)
- Example: ligand binds to 7-pass membrane receptorcatalyzes GTP exchangeto Ga-subunit of trimeric G-proteinactive Ga-subunit-GTP is allosteric activator ofeffector enzymes:
- ADENYLATE CYCLASE: makes cyclic AMP- PHOSPHOLIPASE C: makes DAG and IP3
these second messengers activate target enzymesTrigger cascades cascades
- Must shut off cascade: removal of ligand, hydrolysis of GTP,phosphodiesterase, protein phosphatases, Ca++ ion pumps