Quiz 4 - Biosignaling, Carbohydrates Flashcards
6 Requirements for effective signal transduction
- Specificity
- Amplification
- Modularity - discrete components that interact
- Integration - Different signals combine to create response
- Feedback
- Fidelity - doesn’t decay over time and space
Autocrine
Signals bind to same cell
Paracrine
Signals bind to nearby cell
Synaptic
Involve signals crossing narrow synapse
Endocrine
Signals travel in bloodstream to distant targets
4 Components of Signal Transduction
- Signal
- Receptor
- Transduction Pathway
- Target
3 Types of signals
- Soluble - Proteins, amino acids, lipids, fatty acids, carbohydrates
- Linked - Integrins
- Physical - mechanical, light, temperature
G Protein-Coupled Receptors
External ligand binds to receptor, activates GTP binding protein that regulates another enzyme that creates intracellular second messengers
Receptor Tyrosine Kinase
Ligand binding activates TYR Kinase activity and autophosphorylation
Receptor Guanylyl Cyclase
Convert GTP to cGMP second messenger
Gated Ion Channel
Open or close in response to concentration of signal ligand or membrane potential
Adhesion receptor (integrin)
Interact with things out in the ECM and affect the cytoskeleton
Nuclear receptor
Hormones enter the nucleus through the membranes and bind to DNA
Dissociation Constant (Kd)
Measure of amount of bound ligand compared to free.
High affinity receptor requires little ligand to reach dissociation (low Kd)
Low affinity receptor requires more ligand to reach dissociation
4 roles of plasma membrane in signaling
- Receptor Localization
- Ligand Exposure
- Signaling Complex Formation
- Endocytosis
Protein Scaffold
Protein binds a series of signaling proteins together at the membrane to speed up signaling. Ex.) AKAP5 scaffold protein
Signaling Endosome
Small membrane bound endosomes that group signaling proteins
Lipid raft types and functions
- Calveolar - Calveolin creates a dip in the membrane
- Planar - level with rest of membrane
A. Signal promotion - groups signaling proteins together
B. Signal inhibition - separates proteins to prevent signaling
Endocytic Pathway
Sort internalized vesicles Vesicular Fusion and Excision Transport can occur between every compartment Rab GTPase proteins critical pH decreases along pathway
Endocytic pathway spatially and temporally regulates signaling
- Signal downregulation - endocytose and degrade or re-exocytose a receptor
- Signal maintenance - Increases concentration of receptor and ligand by reducing volume
- Signal generation - When downstream components of pathway are not membrane bound, endocytosis can bring signal to the enzymes
Signal transduction process
First messenger -> Receptor -> Signal Transducer -> Primary Effector -> Second Messenger -> Secondary Effector
How do chemical reactions transfer information?
- Complex formation or dissociation
- Structural change
- Post-translational modification
Post-Translational Modifications
Phosphorylation - kinase Ubiquitination - ubiquitin ligase Glycosylation Oxidation Methylation - methyl-transferase Acetylation - acetyltransferase SUMOylation
Mitogen-Activated Protein Kinase (MAPK) Signaling
Monomeric GTP-ase activates MAP Kinase kinase kinase > MAP kinase kinase > MAP kinase > downstream chain
Ex.) Insulin activating transcription
Janus Kinase (JAK-STAT) Signaling
Janus kinase dimer binds to a cytokine > STAT is phosphorylated > STAT enters nucleus and affects transcription