Exam 2 - Intracellular Signaling Flashcards
What can happen within seconds of IC signaling?
Changes in membrane permeability
What can happen within minutes of IC signaling?
Phosphorylation events
What can happen within hours of IC signaling?
Transcriptional effects
What are the 3 main elements of a signaling pathway?
- Receptor
- Relay/Second messengers/Effectors
- Target protein
What are the 5 classes of cell surface receptors?
- Membrane channels
- GPCRs
- Enzyme-linked receptors
- Pattern recognition receptors
- Cytokine receptors (type of enzyme-linked)
What happens in ion-channel-linked receptor pathways?
Signal molecule (i.e. acetylcholine) binds to receptor and the ion channel opens.
What happens in GPCR pathways?
Signal molecule binds to R, G-protein is activated, enzyme is activated
What happens in enzyme-linked receptor pathways?
Signal molecule in dimer form binds to receptor causing dimerization of receptor; receptors/catalytic domains activate
OR
Signal molecule binds, receptor dimerizes and activates the enzyme
What are pattern recognition receptors important for?
Recognizing foreign invaders
What system are pattern recognition receptors a key part of?
Innate immune system (1st line of defense)
What are toll-like receptors?
Type of pattern recognition receptor that can detect a broad range of pathogens.
What happens in cytokine receptor pathways?
Receptor dimerizes upon binding of a cytokine; cross-phosphorylation of kinases
- Enzyme close but not attached to receptor
What molecule phosphorylates others?
Kinase
What two molecules are exchanged in signaling by phosphorylation?
ATP –> ADP to activate target and vice versa
What two molecules are exchanged in signaling by GTP-binding protein?
GDP –> GTP to activate target and vice versa
What do GPCRs bind?
Trimeric G-proteins
What activates trimeric g-proteins?
GTP binding
What are the two types of trimeric g-proteins?
- Alpha/beta
2. Gamma
What do different GPCR subunits activate?
Different second messengers
What pathway does histamine act thru?
GPCR
Describe the order of the GPCR pathway when histamine binds (4 steps).
- Histamine binds receptor
- PLC activated
- PKC activated and Ca+ released
- Biological activities activated
What do mast cells release?
Histamine granules
What 3 things happen when a mast cell is degranulated?
- Nerve stimulation = itching
- Vasodilation = redness and sometimes heat
- Endothelial gaping and fluid leakage = swelling
How are enzyme linked receptors normally activated?
Signal molecule dimer binds; kinase activity is stimulated by cross-phosphorylation
What pathway uses Ras?
Enzyme-linked
How is Ras activated?
GDP –> GTP; GTP binds to Ras and activates it
What is an example of a hormone that acts through enzyme-linked receptors/Ras?
Growth hormone
What pathway does the MAPK cascade use?
Enzyme-linked/Ras
What does MAPK do?
Phosphorylates many targets to activate them leading to changes in protein activity and gene expression.
How is NF-kappa-B activated?
Toll-like receptor 4 activates signaling cascade; Activated NF-kappa-B and Jun/Fos lead to transcription of target genes
What type of pathway does Jak/STAT follow?
Enzyme-linked (cytokine)
What are the 5 steps to the Jak/STAT pathway?
- Cytokine binds to receptor and Jaks cross-phosphorylate each other
- Activated Jaks phosphorylate receptors
- STATs dock on receptors and are phosphorylated by Jaks
- STATs dissociate from receptor and dimerize via SH2 domain
- STATs bind to promoter region of gene to activate transcription
