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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. G-Protein Linked Receptor Transmembrane Protein (“trans” means “across”, so this protein goes “across” the membrane)
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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 • 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 Receptorsand 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 Receptorsand 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 Receptorsand 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.
G-Protein Linked Receptorsand 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?
Second Messengers • Cyclic AMP • Calcium ions
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