Cell Signaling How to Get a Message from the outside of the Cell to the inside of the cell

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