Cell Signaling Flashcards
What are the three types of short-range signaling?
- Paracrine - secreted signal targets neighboring cells
- Autocrine - signal targets same cell that released it
- Contact-dependent - ligand remains bound to cell surface and interacts directly with receptors on adjacent cells
Wht are the two types of long-range signaling?
- Endocrine - hormones travel to different parts of the body through bloodstream
- Synaptic - occurs between neurons;
What are examples of chemical ligands?
- Ions (e.g., calcium)
- Small molecules (e.g., ACh)
- Peptide and proteins (e.g., growth factors)
- Gases
What are examples of physical signals?
- Light
- Touch
- Heat
Compare hydrophilic and hydrophobic ligands
- Hydrophilic:
• Cannot cross plasma membrane
• Bind to receptors on cell surface - Hydrophobic:
• Freely diffuse through cell membrane
• Bind to intracellular receptors
What are the three types of cell surface receptors?
- Ion-channel receptors
- G protein-coupled receptors
- Enzyme-linked receptors
Describe the two subtypes of ion channel receptors.
- Ligand-gated channels - open when ligand binds to receptor
- Voltage-gated channels - open and close in response to changes in charge difference across membrane
Describe how G protein coupled receptors work.
- Coupled to heterotrimeric GTP-binding protein
- Ligand binding stimulates exchange of GDP in alpha subunit with GTP
- Alpha and beta-gamma subunits dissociate and attach to other effector proteins
Describe enzyme-linked receptors.
• Two forms:
1. Cytoplasmic domain - can function as enzyme
2. Associate directly with intracellular enzymes
• Ligand binding promotes receptor dimerization and enzyme activation
(1) What are internal receptors? (2) Where do they bind to ligand within the cell? (3) What type of response do they trigger? (4) What type of ligands do they bind?
(1) Bind signaling molecules inside cells
(2) cytoplasm or nucleus
(3) Gene expression
(4) Hydrophobic, non-polar molecules diffuse through plasma membrane
Describe an example of ligands that bind to internal receptors and how it leads to a cellular response?
Testosterone (DHT):
* Binds to androgen receptor in cytoplasm
- Travels to nucleus and dimerizes
- DNA-binding site of receptor recognizes and binds to hormone or androgen-response elements
Describe the structure of heterotrimeric G proteins. Compare it in its inactive state vs active state
Inactive state:
• Alpha subunit (GDP bound; bound to beta-gamma-subunit)
• Beta and gamma subunit (always bound together)
Active state:
• triggers GDP/GTP exchange
• alpha subunit dissociates from receptor and beta-gamma subunits
• Alpha and beta-gamma subunits individually bind and activate effectors
What effectors are activated by beta-gamma and alpha, respectively? What second messengers does each effector release?
Beta-gamma —> adenylyl cyclase —> cAMP
Alpha —> phospholipase C-beta —> inositol triphosphate
What are RTKs. Compare them in their inactive and active state.
- Binds ligands (e.g., growth factors)
- Catalyze phosphate transfer from ATP to tyrosine residues
- Cellular processes: growth, differentiation, migration
- Inactive state: monomeric
- Active state: dimeric
What are the two ways RTKs are activated?
- Ligand-induced dimerization - dimeric ligand binds with two RTKs simultaneously to bring them closer
- Receptor-mediated dimerization - monomeric ligand binds each RTK and induces conformational changes to crosslink them together
What is trans-auto phosphorylation?
One RTK phosphorylates tyrosine residues on the other
What two domains can bind to the phosphorylated tyrosine residues?
- Src homology 2 (SH2) domain
- Phospho-tyrosine binding (PTB) domain
What types of responses are mediated by GPCRs?
- Vision
- Smell
- Taste
- Immune response
Explain the two loops of GPCRs.
- Cytosolic loops - bind to G protein
- Extracellular loops - bind to ligan
