Transcript G-Protein-Coupled Receptors

Cell Communication
Chapter 7
7.1 Cell Communication: An Overview
 Cells communicate with one another through
• Direct channels of communication
• Specific contact between cells
• Intercellular chemical messengers
Apoptosis
Fig. 7-1, p. 140
Intercellular Chemical Messengers
 Controlling cell
• Releases signal molecule that causes response
of target cells
 Target cell processes signal in 3 steps:
• Reception, transduction, response
 Signal transduction
• Series of events from reception to response
Signal Transduction
Fig. 7-2, p. 142
Reception
7.2 Cell Communication Systems with
Surface Receptors
 Peptide hormones and neurotransmitters
• Primary extracellular signal molecules recognized
by surface receptors in animals
 Surface receptors
• Integral membrane glycoproteins
 Signaling molecule
• Bound by a surface receptor
• Triggers response pathways within the cell
Surface Receptors
 Cell communication systems based on surface
receptors have 3 components:
(1) Extracellular signal molecules
(2) Surface receptors that receive signals
(3) Internal response pathways triggered when
receptors bind a signal
Peptide Hormones
 Peptide hormones
• Small proteins
 Growth factors
• Special class of peptide hormones
• Affect cell growth, division, differentiation
Neurotransmitters
 Neurotransmitters include
• Small peptides
• Individual amino acids or their derivatives
• Chemical substances
Surface Receptors
 Surface receptors
• Integral membrane proteins
• Extend entirely through the plasma membrane
 Binding of a signal molecule
• Induces molecular change in the receptor that
activates its cytoplasmic end
Response of Surface Receptor
Cellular Response Pathways (1)
 Cellular response pathways
• Operate by activating protein kinases
 Protein kinases add phosphate groups
• Stimulate or inhibit activities of target proteins,
producing cellular response
Cellular Response Pathways (2)
 Protein phosphatases
• Reverse response
• Remove phosphate groups from target proteins
 Receptors are removed by endocytosis
• When signal transduction is finished
Phosphorylation
Amplification
 Each step of a response pathway catalyzed by
an enzyme is amplified
• Each enzyme activates hundreds or thousands of
proteins that enter next step in pathway
 Amplification
• Allows full cellular response when few signal
molecules bind to receptors
Amplification
7.3 Surface Receptors with Built-In
Protein Kinase Activity
 Receptor Tyrosine Kinases
Receptor Tyrosine Kinases
 Receptor tyrosine kinases bind signal molecule
• Protein kinase site becomes active
• Adds phosphate groups to tyrosines in the
receptor itself, and to target proteins
 Phosphate groups added to cytoplasmic end of
receptor are recognition sites for proteins
activated by binding to the receptor
Protein Kinase Activity
7.4 G-Protein–Coupled Receptors
 G proteins: Key molecular switches in secondmessenger pathways
 Two major G-protein–coupled receptor response
pathways involve different second messengers
G-Protein-Coupled Receptors
 G-protein-coupled receptors activate pathways
• Binding of the extracellular signal molecule (first
messenger) activates a site on the cytoplasmic
end of the receptor
G-Protein-Coupled Receptors
Fig. 7-8, p. 147
G-Protein Activation
 Activated receptor turns on a G protein, which
acts as a molecular switch
 G protein
• Active when bound to GTP
• Inactive when bound to GDP
Active G Protein
 Active G protein
• Switches on the effector of the pathway (enzyme
that generates second messengers)
 Second messengers
• Small internal signal molecules
• Activate the protein kinases of the pathway
Response Pathways
Second Messengers: cAMP
 1st of two major pathways triggered by Gprotein-coupled receptors
 Effector (adenylyl cyclase) generates cAMP as
second messenger
 cAMP activates specific protein kinases
cAMP Receptor-Response Pathways
Fig. 7-10, p. 148
cAMP
Fig. 7-11, p. 148
Second Messengers: IP3 and DAG (1)
 2nd major pathway triggered by G-protein–
coupled receptors
 Activated effector (phospholipase C), generates
two second messengers, IP3 and DAG
Second Messengers: IP3 and DAG (2)
 IP3 activates transport proteins in the ER
• Releasing stored Ca2+ into the cytoplasm
 Released Ca2+ (alone or with DAG) activates
specific protein kinases
• Adds phosphate groups to target proteins
IP3/DAG Receptor-Response Pathways
Pathway Controls
 cAMP and IP3/DAG pathways are balanced by
reactions that eliminate second messengers
• Stopped by protein phosphatases that continually
remove phosphate groups from target proteins
• Stopped by endocytosis of receptors and their
bound extracellular signals
Mutations
 Mutated systems can turn on the pathways
permanently, contributing to progression of
some forms of cancer
Gene Regulation: Ras
 Some pathways in gene regulation link certain
receptor tyrosine kinases to a specific G protein
(Ras)
 When the receptor binds a signal molecule, it
phosphorylates itself
• Adapter proteins then bind, bridging to and
activating Ras
Activated Ras
 Activated Ras turns on the MAP kinase cascade
 Last MAP kinase in cascade phosphorylates
target proteins in the nucleus
• Activates them to turn on specific genes
 Many of these genes control cell division
Gene Regulation
7.5 Pathways Triggered by Internal
Receptors: Steroid Hormone Receptors
 Steroid hormones have widely different effects
• Depend on relatively small chemical differences
 Response of a cell to steroid hormones
• Depends on internal receptors and the genes
they activate
Steroid Hormone Receptors
 Steroid hormones penetrate plasma membrane
• Bind to receptors within the cell
 Internal receptors
• Regulatory proteins that turn on specific genes
when activated by binding a signal molecule
• Produce cellular response
Two Domains of
Steroid Hormone Receptors
 Steroid hormone receptors
• One domain recognizes and binds a specific
steroid hormone
• One domain interacts with the controlling regions
of target genes
Gene Activation:
Steroid Hormone Receptors
Cell Response
 Cell response to a steroid hormone
• Depends on whether it has an internal receptor
for the hormone
 Type of response within the cell
• Depends on the genes that are recognized and
turned on by an activated receptor
7.6 Integration of
Cell Communication Pathways
 Cross talk
Cross-Talk
 Cell signaling pathways communicate with one
another to integrate responses to cellular signals
 May result in a complex network of interactions
between cell communication pathways
Cross-Talk
Modification of Cell Response
 Cross-talk often results in
• Modifications of cellular responses controlled by
the pathways
• Fine-tuning effects of combinations of signal
molecules binding to receptors of a cell
Cell Communication Pathways
In Animals
 Inputs from other cellular response systems also
can become involved in the cross-talk network
• Cell adhesion molecules
• Molecules arriving through gap junctions