G Protein-Coupled Receptor - ap

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Cell Communication
Chapter 11 - Abridged
Cell-to-Cell Communication
 Critical for multicellular organisms
 Trillions of cells must communicate in order to
coordinate their activities
 Recent research indicates: cancer results from
corrupted communication
 Unimportant for the AP Exam
 Crucial for understanding the breakthroughs in cancer
and genetics that are occurring almost monthly now
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Recent Nobel Prizes in Medicine
 2001 – Hartwell, Hunt, &
Nurse – cyclin pathways and
cell cycle regulation (yeast)
 2002 – Brenner, Sulston,
Horvitz – used C. elegans to
elucidate the mechanism of
apoptosis
 2006 – Fire & Mello - used
C.elegans to discover the
pathway of RNA interference
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Simon Sez…
 Signaling is a lot like the game “Simon Says…”
 The signal is received: the game players hear: “Simon
says take a step forward”
 The signal is transduced: players must decide whether
to step forward or not
 The signal elicits a response: players step forward if the
command was preceded by “Simon says”
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3 Stages of Signaling
 Thesis: external signals are received & converted to
responses within the cell
1. Reception
 Signaling molecule binds to receptor protein = Shape Change
2. Transduction
 Cascades of molecular interactions relay signals from
receptor proteins to target molecules in the cell
3. Response
 Regulation of transcription or cytoplasmic activities
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1st form of signaling
 Yeast (fungi) mating
Process:
1.Release mating factor
2.Receive complementary
factor
3.????
4.Response: grow toward
opp. Type
5.Nuclei fuse = genetic
recombination
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Overview of Cell Signaling
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View Animation
 11_06 SignalingOverview_A.swf
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Reception
 Reception involves getting the signal to the correct
receiver
 Only certain cells have the correct receptor = only
certain cells can receive the signal
 Signaling molecule usually called ligand
 receptor-ligand binding causes a conformational change
in the receptor molecule (remember induced fit?)
 Conformational change = Activation of the receptor
molecule
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2 Types of Signal Receptors
1. Plasma Membrane Receptors
 Hydrophilic or water-soluble ligands or signal molecules
 G Protein-Coupled Receptors (GPCR)
 Receptor Tyrosine Kinase (RTK)
 Ion Channel Receptors
2. Intracellular Receptors
 Hydrophobic or Nonpolar ligands
 Carry out transduction by themselves
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View Animation
 11_13SignalTransduction_A.swf
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G Protein-Coupled Receptor
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Receptor Tyrosine Kinase (RTK)
 Amplification
 Kinase = enzyme
for transfer of
phosphate group
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Ligand-Gated Ion Channel
 Membrane receptor with a region
that acts as a “gate” when the receptor
changes shape.
 When the signal molecule binds,
gate opens or closes
 Important in the nervous system
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Intracellular
Receptor
 Hydrophobic signal molecules
 Testosterone
 Most intracellular receptor
signals do the entire transduction
on their own
 Testosterone behaving as a
transcription factor
-- controls which genes (DNA)
are transcribed into mRNA
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Transduction
 Multistep Pathway
 Transduction = shape change
 Signal amplification
 Signal Transduction Pathways often
involve a phosphorylation cascade
 Molecule is phosphorylated = activated
 Phosphate removed = deactivation
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Protein Kinases (PK)
-- enzymes that transfer
phosphate groups
Protein Phosphatases (PP)
-- enzymes that remove
phosphate groups
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Second Messengers
 1st messenger = receptor
 Only GPCR & RTK have 2nd messengers
 Other important component of transduction pathways
 Most components are enzymes or proteins
 Small & polar
 Calcium Ions & Cyclic AMP
 Initiate a phosphorylation cascade
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Response
 Response may occur in the cytoplasm or nucleus
 2 Types of typical response:
1. Enzyme activity is regulated (turned on or off)
2. Synthesis of enzymes is regulated (promoted or inhibited)
 Transcription Factors – control which genes are
transcribed (DNA  RNA)
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Transcription
Factors
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GF = Growth
factor
RTK = Receptor
Tyrosine Kinase
Ras = G Protein
Associated with
tumor growth
Rho = G protein
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RTK = Receptor
Tyrosine Kinase
GPCR – G-protein
coupled receptor
PDK1 = Protein
dehydrogenase
kinase
Akt = Protein kinase
-- Involved in apoptosis
Apoptosis =
Programmed cell death
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Day 1 Complete
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