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

1. Reception 2. Transduction 3. Response

G-Protein Linked Receptors 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 Process 1. Reception 2. Transduction 3. 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