GPCRs all share a common structure with 7 TM domains

1
GPCRs all share a common structure with 7 TM
domains
Figure 20-10
2
F. Campagne, J.M. Bernassau, B. Maigret
3
Trimeric Gs protein links GPCRs and Adenylyl
Cyclase
Figure 20-16
4
GPCRs act through 2nd Messengers
cAMP and cGMP are both rapidly degraded By
respective PHOSPHODIESTERASE ENZYMES
Figure 20-4
5
The Basic cycle for GPCR coupled G-proteins is
sensitive to the effects of agents such as
Cholera toxin (the product of Vibro cholera and
the source of cholera) which causes persistent
activation of AC in intestinal epithelial cells
leading to massive H2O uptake and diarrhea
Figure 20-17
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Hormone Induced Activation and Inhibition of AC
Through Gas and Gai
Gai is the target of Pertussis toxin (product of
Bordella pertussis bacteria). ADP-ribosylation of
Gai locks it in GDP bound form-WHOOPING COUGH
Figure 20-18
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Different AC isoforms respond to alternate
G-protein subunits
Figure 20-43
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Many types of G-proteins with alternate Ga
subunits
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Domain Swapping experiments with chimeric GPCRs
demonstrate functional domains as well as the
conservation of motifs!
Figure 20-14
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DownstreamCREB links cAMP signals to gene
transcription. To do this, cAMP acts to modulate
the activity of the Allosteric Enzyme cAPK (PKA)
Figure 20-48a
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Phosphorylation of GPCRs modulates their activity
Homologous vs Heterologous Desensitization
Figure 20-47
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Arrestins Bind to GPCR-P and target them for
Endocytosis as well as build SCAFFOLDS that
link GPCRs to other Signaling Pathways
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cAPK (PKA) different target proteins are found
in different cell types
One example is glycogen metabolism PKA kinases
glycogen phosphorylase kinase which kinases
glycogen phosphorylase which converts glycogen to
glucose. At the same time, PKA targets Glycogen
synthetase to INACTIVATE the synthesis of more
glycogen whilst PKAs target of Protein
Phosphatase inhibitor prevents its action to
reverse everything.
Figure 20-35
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Once AC Is De-Activated cAMP Levels Drop and the
Process Is Reversed
Figure 20-35b
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cAPK/PKA Acts Via a Specific Inhibitor (IP) Which
is Activated by Phosphorylation to Effectively
INHIBIT the Activity of PP (Phosphoprotein
-Phosphatase)
Figure 20-36
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Other Important 2nd Messenger Systems
Figure 20-38b
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Goa or Gqa G-protein subunits mediate GPCR
signals to activate PLCb on cytoplasmic surface
to yield IP3 DAG
Figure 20-38a