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Cell SignalingCell SignalingHow to Get a Message from the outside of
the Cell to the inside of the cellHow to Get a Message from the outside of
the Cell to the inside of the cell
1. Reception2. Transduction3. Response
G-Protein Linked Receptors
• G-Protein Linked Receptor• Transmembrane Protein (“trans”
means “across”, so this protein goes “across” the membrane)
• 7 Alpha helices• Outside: Signal molecule binding
site.• When a signal molecule (also
called a ligand) binds to the signal binding site, this causes the G-Protein Linked Receptor to change shape• e.g. this signal molecule can be
epinephrine (adrenaline)• Inside: Changes in G-Protein
linked receptor causes another molecule called a G-Protein to change from an inactive to an active state.
G-Protein Linked Receptors
and G-Proteins• G-Protein Linked Receptor is
different from a G-Protein (see illustration)
• G-Protein Linked Receptor• A transmembrane protein-
introduced in the last slide• Detects the signal and
changes shape (hence the name “receptor”)
• Has “G-Protein” as part of the name because it will also bind with a “G-Protein” inside the cell
• G-Protein• Named “G-protein” because
GDP is bound to it (GDP is similar to ADP)
• Located on the inner membrane of the cell
• When GDP is bound to it, it is in its inactive state
G-Protein Linked Receptors
and G-Proteins• Process:• Signal molecule binds to
G-Protein Linked Receptor
• G-Protein Linked Receptor changes shape
• G-Protein Linked Receptor binds to G-Protein (which is inactive)
• G-Protein Activation causes GDP to be replaced by GTP
• G-Protein with GTP is now in its active form
G-Protein Linked Receptors
and G-Proteins•G-Protein dissociates
from the G-Protein Linked Receptor
•G-Protein diffuses along the membrane• Binds to an enzyme• This binding activates
the enzyme• Results in a cellular
response.
CELLULAR RESPONSE AND THE Second Messenger
•Adenylyl Cyclase is a common enzyme in these signally pathways• It catalyzes the
conversion of ATP to cyclic AMP
• Cyclic AMP (cAMP) is known as a second messenger
Second Messenger•Adenylyl Cyclase
• Enzyme that catalyzes ATP->cyclic AMP
• Cyclic AMP (cAMP) is the second messenger• See structure below
Second Messenger
• cAMP activates another protein• Protein Kinase A
Phosphorylation Cascade•Protein Kinase
• Enzyme that catalyzes the transfer of phosphate groups from ATP to a protein
• 2% of our genome codes for these enzymes!!
Phosphorylation Cascade•Protein Phosphatases
• Enzyme that catalyzes the removal of phosphate groups from proteins
• Reverse of what protein kinases do.
Epinephrine
G-Protein Linked Receptors
and G-Proteins• G-Protein Inactivation• G-Protein acts as
GTPase• Breaks down GTP to
GDP• Unbinds from
enzyme• Becomes inactive
again
Three Step Process1. Reception2. Transduction3. Response
Animations
G-Protein Cell Signaling
Is Cell Signaling Important?Earl Sutherland discovered how
epinephrine (adrenaline) works to increase glucose to
the cells to aid in the “fight or flight
response.”-Free Response #1
tonight
G-Protein Linked Receptors• Are G-Protein Linked Receptors really
that important?
Tyrosine-Kinase Receptors
Tyrosine-Kinase Receptors
Tyrosine-Kinase Receptors
Tyrosine-Kinase Receptors
Ion Channel Receptors
Ion Channel Receptors
Ion Channel Receptors
Second Messengers
• Cyclic AMP• Calcium ions
Calcium Ions
Calcium Ions and IP3
Growth Factors and Stimulation of Transcription
Signal Molecules• G-Protein Linked Receptors
• Hormones, neurotransmitters, odors, light sensitive compounds
• Involved in bacteria infections• 60% of all medicines today exert their
effects by influencing G-protein pathways.
• Two Principle Signal Transduction Pathways• Cyclic AMP signal pathway• Phosphatidylinositol (PIP) signal
pathway• Tyrosine Kinase Receptors
• Growth factors (cell growth, cell reproduction) hormones (insulin), cytokines, can cause cancer