Signal Transduction Flashcards
List five types of cell-cell communication and describe them.
Endocrine
- endocrine cell secretes hormone into bloodstream to signal target cell
Paracrine
- signalling cell neighbors target cells and sends signal (local mediator) to target cells
Neuronal
- …It’s a neuron.
Contact-Dependent
- Signalling cell has a membrane-bound signal molecule. Must make contact with target cell.
Autocrine
- Cell signals itself (cancer cells and other normal cells)
Define Signal Transduction.
Conversion of extracellular signals into intracellular events.
Describe the basic pathway of Signal Transduction.
- Receptor binds a ligand (primary messenger)
- Signal transduction via intracellular signalling molecules, second messengers, amplification.
- Cell responds
- Gene expression changes.
What are the two types of Intracellular Signalling Proteins?
Kinases
GTP Binding Proteins (G-Proteins)
What is Signal Amplification?
A small signal produces a large cellular response. The amplification can result from second messenger production/kinase activation.
What are the kinds of Receptors involved in Cell Signalling?
Surface Receptors:
- G-protein coupled Receptors (GPCR)
- Receptor Tyrosine Kinases (RTK)
- Serine/Theonine Kinase Receptors
- Receptors without kinase activity
- Ion Channel-linked Receptors
Intracellular Receptors
- Steroid Hormone Receptors
Not super high-yield
Name the 4 classes of membrane receptors and describe their action upon receiving a signal.
Ligand-Gated Channel (open/closes channel) Receptor-Enzyme (activates bound intracell enzyme) G-Protein Coupled Receptor (open ion channel or alter enzyme activity) Integrin Receptor (alters the cytoskeleton)
Which subunit of a heterotrimeric G-Protein typically has the GDP/GTP bound to it?
Alpha subunit.
Walk through the mechanism of GPCR activation.
- Ligand binds receptor (G-protein attaches to receptor if it wasn’t already), altering conformation to activate G-protein.
- GDP on alpha subunit replaced with GTP
- GTP causes G-protein to break into alpha and Beta-Gamma groups, exposing sites to bind to effectors
- alpha or Beta-Gamma subunits interact with an effector to modulate its activity
- alpha subunit has GTPase activity (hydrolyzes GTP to GDP)
- GDP on alpha reassociates G-protein, leaving effector and ending signal.
What are the two major pathways that use GPCR and G-Proteins?
cAMP 2nd messenger pathway
DAG and IP3 2nd messenger pathway
Describe the cAMP pathway.
- Signal binds to GPCR, activating G-Protein
- G-Protein activates adenylyl cyclase (amplifier enzyme)
- Adenylyl cyclase converts ATP to cAMP
- cAMP activates protein kinase A (pKA)
- pKA phosphorylates other proteins, leading to a cellular response
- pKA also enters nuclease and phosphorylate (activate) transcription factors (CREB) to bind to CRE (cAMP Responsive Element) in promoter of cAMP-responsive genes.
- cAMP phosphodiesterase catalyzes cAMP into 5’AMP, ending response.
What activity can the alpha subunit have?
Inhibitory (Gi) or Stimulatory (Gs). Both involve activation by a bound GDP converting to GTP.
What toxins cause an increase of cytosolic cAMP and signalling? Describe their different mechanisms.
Cholera (lock Gs into active state by blocking GTPase activity
E.Coli toxin (same as Cholera)
Pertussis toxin (Locks Gi into GDP-bound inactive state
Describe the DAG and IP3 pathway.
- Gq activates G-Protein (Phospholipase C)
- PLC breaks down inositol phospholipid into second messengers IP3 and DAG
- IP3 induces Ca2+ release from sER
- Both DAG and IP3 activate PKC, which activates transcription factors.
What is the Pathology of Retinitis Pigmentosa 4?
Defect: mutated Rhodopsin (rod pigment)
- results in degeneration of photoreceptor cells)
Symptoms: loss/diminished night and peripheral vision.
