1451792
| Question | Answer |
| How do hydrophilic hormones work? | - Can't diffuse across the PM - Need to interact w/ protein on the PM - That protein changes conformation - Induces change in the cell |
| How do hydrophobic hormones work? | - Receptors within cells - Receptors act as transcription factors - Must be activated by ligands - Result in changes in expression |
| Define a receptor. | Binding protein in/on cell interacts with H in highly specific manner Elicits a characteristic response |
| What are 5 characteristics of receptors? | 1. High affinity - holds on stronger, holds on longer 2. High specificity - ensures only intended H interacts 3. Saturable - add more H, no more response after a point 4. Reversible 5. Tissue distribution appropriate for H function |
| How are receptors regulated? (3) | 1. Regulation of affinity - phosphorylation (change conformation, change affinity) - Dimers/oligomers (higher affinity when formed) 2. Change in # of receptors - at genetic level - degradation 3. Regulation of Receptor-Effector coupling - break apart = termination of activity - desensitization |
| Describe the process of degradation. | Internalization - ligand binds receptor, gets internalized by endocytosis pH level causes uncoupling of complex 2 options: 1. Receptor gets degraded by lysosome 2. Receptor recycled (usu. w/ transporter receptors that bring it across the PM) |
| How does desensitization work? | Only in peptide H Results from degradation/receptor transduction uncoupling Desensitization: phosphorylation of receptor by BARK + recruitment of arresting protein (e.g. chemical castration) |
| What are the five main types of receptors? | 1. Cell surface 2. Enzyme linked 3. Ion channel receptor 4. Intracellular (nuclear) 5. Signal transduction (non-genomic) |
| Describe cell-surface receptors. | - for hydrophilic H - G-protein linked - involves recruitment of second messengers |
| What are the two possible signal transduction pathways? | 1. H binds receptor Adenylate cyclase (AC) activates cAMP PKA phosphorylates a substrate for a response 2. H binds receptor Phospholipase C (PLC) turns phospholipids into either DAG or IPG DAG: PKC phosphorylates substrate for response IPG: releases Ca, which acts on DAG |
| What is the structure of G-protein-linked receptors? (4) | 1. Single-chain peptide 2. 7 transmembrane domains 3. Extracellular ligand binding site 4. Intracellular G-protein coupling site |
| Describe G-proteins and their function. | - have alpha, beta, gamma subunits - couple a membrane-bound receptor to intracellular receptors - forms heterotrimer of alpha, beta, gamma - dissociation of alpha from beta-gamma at GTP binding (binding inactivates alpha) |
| What are the three G-protein families and what do they do? | Gs - activates cAMP pathway Gi - deactivates cAMP pathway Gq - phospholipid pathway |
| How is cAMP formed? degraded? What does it activate? What are its responses? (5) | formation: adenylate cyclase (AC) catalysis degradation: phosphodiesterase activates PKA, leading to cellular responses 1. enzyme activation 2. protein synthesis 3. muscle relaxation 4. nerve stimulation 5. hormone secretion |
| How does PKA initiate protein synthesis? | Phosphorylates CREB (the protein that recognizes and binds) i.e. the transcription factor |
| Describe the phospholipid pathway. What activates it? | Activated by Gq DAG becomes AA, catalyzed by DG lipase AA catalyzed by PLA2 to create phospholipids |
| What is IP3? What does it do? | Inositol triphosphate Activates Ca channel, Ca released form smooth ER Binds channel, letting Ca out Ca activates DAG |
| What is DAG? What does it do? | Diacylglycerol Changes into prostaglandin group of H Activates PKC and its substrates Activated by IP3 release of Ca Acts on Arachidonic acids (AA) |
| What is AA? What does it do? | Arachidonic Acid Releases Ca form ER Gets acted on by DG to form phospholipids |
| What are some features of enzyme-linked receptors? (4) | - key domain: intracellular region that either has its own enzyme activity or is associated w/ an enzyme - recognize various enzymes - have extracellular H-binding domain - Single transmembrane domain |
| What are the 4 categories of enzyme-linked receptors? | 1. Tyrosine kinase receptors 2. Tyrosine-kinase-associated receptors 3. Serine-Threonine Kinase receptors 4. Guanylate cyclase receptors |
| What are 3 main tyrosine kinase receptors? | 1. EGF-R: part of phospholipid pathway 2. PDGF-R: 2 different subunits 3. Insulin-R: unique |
| How do the Tyrosine Kinase Receptors work? | Hormone binding triggers dimerization (homodimerization) Receptor autophosphorylates the other subunit Phosphorous residues on receptor MC act as site of protein binding |
| Describe the Insulin-R receptor | - A tyrosine kinase receptor Alpha - ligand binds Beta - transmembrane kinase domain - has alpha and beta subunits joined w/ disulphide bonds i.e. a-a and b-b to form a receptor complex, even in absence of H Receptor recruits a docking protein, Insulin Receptor Substrate 1 (IRS-1) to get: - protein-protein interaction - Kinase phosphorylates dimer |
| Describe the Map Kinase pathway | - Takes place on EGF-R GRB2 Binds SOS Helps activate a G-protein (i.e. GDP exchanged for GTP) Activates Ras Ras activates kinase Activates another kinase Activates effector proteins E.g. Transcription factors, receptor MCs - Ras turns off when GTP --> GDP GTPase activates protein |
| How do the Tyrosine Kinase-Associated Receptors work? Give an example | - Interact w/ GH, PRL - Receptors have no kinase activity themselves - Ligand binding triggers coupling of receptor to tyrosine to kinase Substrates phosphorylated e.g. STAT2 (TF) gets phosphorylated, then regulates gene expression |
| How do the Serine-Threonine Kinase Receptors work? Describe the ligands | TGF beta superfamily mediates signalling Ligands have Type I and II receptors, and associated SMADs Types I and II come together to form a receptor complex 2 subfamilies: 1. TGF-Beta family 2. BMP family |
| Describe what the TGF-Beta family is and how it works. | - part of Serine-Threonine Kinase receptor H binds Type II first, then recruits Type I Active when phosphorylated Activates downstream molecules |
| Describe what the BMP family is and how it works. | High affinity for type I receptor, low for Type II Ligand binds w/ both at the same time |
| What is R-SMAD? When is it activated? | Receptor-regulated SMAD Activated when complexes w/ another SMAD, Co-SMAD |
| What are SMADs, in general? | Act as transcription factors, either alone or with a partner, bind to DNA |
| What is Co-SMAD? | Common SMAD Activates other SMADs |
| What is an Inhibitory SMAD? | Inhibits process of interaction b/w R and Co-SMAD |
| What do does Guanylate Cyclase (GC) catalyse? | GTP --> cGMP |
| What is sGC? How is it activated? | Soluble GC Activated by NO |
| What does NO do? What does it activate? | Very potent, especially in the vascular system Enters cells, directly activates GC |
| What is pGC? What is it a receptor for? | Particulate GC Receptor for natriuretic factor. |
| How are ion channel receptors activated? | Activated by ligand-binding, mostly neurotransmitters with rapid responses |
| What is the typical ion channel receptor pathway? | Signal > R > conformational change of R > channel opens > ions flow in (Na, K, Ca) |
| What are common features of ion channel receptors? (4) What is an example? | 1. Multiple subunits 2. Each subunit has 4 transmembrane domains 3. N and C terminals are extracellular 4. Second transmembrane domain contributes most strongly to pore formation E.g. NAChR - Nicotinic acetyl choline receptor |
| What is the typical intracellular (nuclear) receptors pathway? | H enters target cell by diffusion Binds receptor MC Receptor gets activated to DNA binding form H-R complex binds to HRE, activates transcription |
| What are the 6 domains of Intracellular (nuclear) receptors? | A and B: Transcription activating C: DNA-binding D: Nuclear localization signal E: Ligand-binding domain F: C-terminal (function not clear) |
| What is the function of the DNA-binding section in Intracellular Receptors? | Recognizes and binds a specific DNA sequence, i.e. the hormone response element (HRE) |
| What is the function of the Nuclear localization signal in Intracellular Receptors? | Protein made in the cytoplasm that can transfer into the nucleus |
| What is the function of the Ligand-binding domain in Intracellular Receptors? And what does it activate? | Region-specific intermediary between the hormone and the receptor activates: transcription dimerization heat-shock-protein-binding |
| What conformational changes does the intracellular (nuclear) receptor molecule undergo in order to be in its DNA-binding form? | - more compact/protease resistant - dissociates from inhibitors (e.g. hsp 90) - dimerization - phosphorylation |
| What groups use the intracellular (nuclear) pathway? | Steroids TH: T3 and T4 1,25 (OH)2 Vit D3 |
| What would be a way to test if a hormone had a non-genomic action? | Block transcription/translation and see what happens If action still takes place, then it's non-genomic |
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