Term
| What are the 7 steps of cell signaling? |
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Definition
| "(1) Synthesis of signal molecule, (2) Exocytosis of signal molecule, (3) Transport to target cell, (4) Binding of signal to receptor, (5) Initiation of signal-transduction pathways, (6) Intracellular changes, (7) Removal of signal" |
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Term
| What are the three ways signal transduction pathways can be named? |
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Definition
| "(1) Signal molecule (ligand), (2) Receptor, (3) Key intracellular signal transduction component; The same pathway may have many names!" |
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Term
| What are some possible signal molecules? |
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Definition
| "Proteins, steroids, lipid derivatives, gases, physical stimuli (light), etc." |
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Term
| Signalling by plasma membrane-attached proteins is a special type of _______ signalling. |
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Definition
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Term
| Describe ENDOCRINE signaling: |
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Definition
| Signaling from a distance via the bloodstream; Signal molecule is in LOW CONCENTRATION and the receptor has a HIGH AFFINITY (example = hormone) |
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Term
| Describe EXOCRINE signaling: |
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Definition
| Signaling from close proximity via diffusion; Signal molecule is in HIGH CONCENTRATION and the receptor has a LOW AFFINITY (example = neurotransmitters and growth factors) |
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Term
| Describe PARACRINE signaling: |
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Definition
| "Signaling within the same cell, example is growth factors" |
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Term
| What are the three discrete domains of a cell surface receptor? How are these affected by ligand binding? |
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Definition
| "extracellular, transmembrane, cytosolic domains; Ligand binds and induces a conformational change in the extracellular domain which is transferred through the transmembrane domain to the cytosolic portion." |
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Term
| What is the formula for Kd and how is this related to binding affinity? |
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Definition
| "Kd = [receptor][ligand]/[receptor-ligand complex]; high Kd = low affinity, low Kd = high affinity" |
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Term
| How many receptors must be activated to induce a maximum physiological response (generally)? |
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Definition
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Term
| What two factors determine the sensitivity of a cell to external signals? |
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Definition
| (1) Number of receptors and (2) Affinity for the ligand |
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Term
| What are two ways to isolate receptors from cell membranes? |
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Definition
| "(1) Mix cells with a radiolabeled ligand and wash them with a detergent, then run them in an affinity chromatography column; (2) Express cDNA for the receptor proteins in cells and do affinity chromatography column" |
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Term
| What are the two types of cellular responses induced by signalling molecules? |
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Definition
| "(1) Changes in activity/function of pre-existing proteins (via G-proteins, fast!); (2) Changes in the amounts of specific proteins in the cell (genetic changes, slow!)" |
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Term
| What is a secondary messenger? |
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Definition
| "A non-protein, low MW intracellular signalling molecule that are increased or decreased in concentration when ligands bind to receptors. They bind to other signaling proteins in the cascade and regulate their activities." |
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Term
| What is the general structure of a G-Protein Coupled Receptor (GPCR)? |
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Definition
| "7 transmembrane regions with the N-term on the extracellular face and the C-term on the cytosolic face; Can be TRIMERIC (alpha, beta, gamma subunits) or MONOMERIC (Ras)" |
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Term
| What is the basic sequence of events in activation of a trimeric G-protein? |
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Definition
| "Receptor becomes activated, G-protein binds to the receptor, receptor causes dissociation of GDP from alpha subunit and induces GTP binding to the alpha subunit which makes the alpha subunit dissociate from the beta and gamma subunits. Activated alpha subunit travels downstream to effector proteins in the membrane." |
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Term
| How did the Fluorescence Energy Transfer experiments prove the G-protein mechanism? |
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Definition
| "If the alpha subunit is detached from the beta and gamma, it will emit blue light. This happened when the ligand was present. If the alpha subunit is attached to the beta and gamma subunits, it will emit a yellow light. This happened when the ligand was not present." |
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Term
| Explain how G-proteins can regulate K+ ion channels in response to Ach in cardiac muscle cells: |
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Definition
| "Acetylcholine binding to its receptor, G-protein binds to receptor, the receptor causes the activation (with GTP) of the alpha subunit BUT the beta/gamma subunits dissociate and travel downstream to bind to the K+ channels when the alpha subunit is activated!" |
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Term
| How do G-proteins act in the light-activation of Opsin in rod cells of the eye? |
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Definition
| "Light activates opsin, opsin is the receptor which activates the alpha subunit, alpha subunit travels downstream and activates PDE (phosphodiesterase), PDE converts cGMP to GMP, reducing the amount of cGMP in the cell which causes the ion channel to remain closed when light is present |
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Term
| How does cAMP activate Protein Kinase A (PKA)? |
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Definition
| cAMP binds to PKA and releases its catalytic subunits to activate it. |
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Term
| "When G-proteins activate or inactivate Adenyl Cyclase, what secondary messenger is affected?" |
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Definition
| "cAMP, which activates Protein Kinase A" |
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Term
| What is the signal transduction pathway when G-proteins activate Phospholipase C? |
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Definition
| "Phospholipase C splits PIP2 into IP3 and DAG which do 2 things: (1) IP3 Opens Ca++ channels in ER, (2) DAG activates Protein Kinase C (PKC) in the cell membrane, which starts a cascade |
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