Lecture 9 - Receptors & Signal Transduction Flashcards
how do hormones signal (4)
- Hormone binds to receptor
- Changes the conformation and activity of the receptor
- Alters the activity of intracellular signaling pathways
- Leads to change in synthesis of target proteins (slow) and/or modification of existing target proteins (fast)
what characteristics do receptors have (6)?
- size of protein
- grouped?
- receptor and ligand numbers?
- behaviour of function
- location (3)
- Large proteins
- grouped in families
- Can be multiple receptors for one ligand or more than one ligand for a receptor
- Variable number of receptors for a target cell (~500-100,000)
- Can be activated and inhibited
- Located in cell membrane, cytoplasm, nucleus
what are the four main properties of receptors?
- high affinity for ligand
- saturable
- specific
- reversible
what does “cellular receptors are saturable” mean?
- the more a ligand it added, the more receptors will be filled
- however, there comes a point where too much of the ligand is added and the # of filled receptors plateaus
- this is because there isn’t enough free receptors remaining for the ligand to bind, thus not increasing in number.
what are the two main types of receptors?
1) Intracellular receptors (lipophilic hormones/signals –> enters the cell through the membrane - receptor protein inside)
- Cytosolic and nuclear
- Directly alter gene transcription = genomic
effects
- ex lipophilic steroid hormones
2) Plasma membrane receptors (hydrophilic hormones/signals –> bind to receptor protein on membrane because cant enter)
- G protein-coupled receptors
- Receptor-enzyme receptors
- Receptor-Channel
- Integrin Receptor
- ex hydrophilic peptide hormones
how do peptide and steroid hormones react differently with their receptors?
- Peptide hormones
– Cannot penetrate target cell
– Bind to surface receptors and activate intracellular
processes through second
messengers - Steroid hormones
– Penetrate plasma membrane and bind to internal receptors (usually in nucleus)
– Influence expression of genes of target cell
– Take several hours to days to show effect due to lag for
protein synthesis
intercellular receptors:
how is the hormone response element triggered by lipophilic hormones/stimuli?
- a lipophilic hormone is able to enter the cell via diffusion
- it enters the cytoplasm then enters the nucleus where it will bind to the receptor to form a hormone-receptor complex
- it does this so it can affect the target cells expression of its gene (whole point of the hormone)
- thus the hormone receptor complex binds to the hormone response element (HRE) = specific DNA sequence on the DNA in the nucleus
- this hormone can either behave as an activator or repressor for transcription on the HRE, dependent on what the cell needs at that time
- only the genes that are a part of the HRE will be activated or repressed after the complex binds (if the purpose is to inhibit, co-repressors may be recruited by the receptor to inhibit transcription)
extracellular receptors: there are many membrane receptors but what are the two that we will focus on and what is there function in one brief sentence
G protein-coupled receptor
- Ligand binding to a G protein-coupled receptor opens an ion channel or alters enzyme activity.
Receptor-enzyme
- Ligand binding to a receptor-enzyme activates an intracellular enzyme –> catalytic receptor
what property do ion extracellular receptors change in the cell
- the electrical property
- ions move in and out changing membrane potential
what are g protein-coupled receptors?
- structure
- what is a common G-protein system that is used as a signal transduction system (define)
- what are common second messengers that g proteins use (define)
- they are 7 membrane spanning proteins
- they have a cytoplasmic tail linked to G protein, a three part transducer molecule (G-proteins act as intermediaries between receptors on the cell surface and internal cellular pathways).
- a key system for signal transduction for many protein hormone is the G protein-coupled adenylyl cyclase-cAMP system
- these G-protein coupled receptors use some lipid second messengers: Once the receptor is activated by the first messenger, it triggers the production or release of a second messenger inside the cell. These second messengers help propagate and amplify the signal.
when g proteins are activated what do they do (2)
– Open ion channels in the membrane
– Alter enzyme activity on the cytoplasmic side of the
membrane
Gs: generally explain how the Gs protein-coupled receptors send a signal in the cell
- messenger binds to the g protein-coupled receptor (GPCR) on the cell membrane
- there is an alpha, beta, and gamma section on the G protein that is bound to the GPCR on the inside. the alpha protein has certain subtypes (s, i, q – here s is whats triggered since its Gs) that has enzymatic activity.
- here Gs exchanges the GDP attached to it to GTP. - the GTPs-alpha complex binds to the adenylate cyclase membrane protein (an amplifier enzyme) and activates it
- adenylyl cyclase converts 1 ATP to 3 cyclic AMP
- cyclic AMP activates 3 protein kinase A (PKA)
- Protein kinase A phosphorylates other proteins (3x the amt of PKA), leading ultimately to a cellular response (amplification– 1 signal molecule leads to so many cell responses)
Gs: what is the main unit that amplifies target cell responses
what is amplification?
Second messengers such as cAMP amplify target cell responses
1 signal –> so many messengers
Gq: generally explain how the Gq protein-coupled receptors send a signal in the cell
- messenger binds to the g protein-coupled receptor (GPCR) on the cell membrane
- there is an alpha, beta, and gamma section on the G protein that is bound to the GPCR on the inside. the q subtype in the alpha section is whats relevant here
- the Gq alpha protein activates phospholipase C (PL-C) an amplifier enzyme
- PLC does two things:
(a) it converts membrane phospholipids into DAG which stays in the membrane and activates protein kinase C, which in turn phosphorylates proteins and activates cellular responses
(b) PLC converts membrane phospholipids into IP3 which diffuses into the cytoplasm and causes the release of Ca2+ from the ER into the cell for a cellular response
Gi: what does Gi protein-coupled receptors do and whats its pathway
i for inhibitory
when a messenger binds to the g protein-coupled receptor (GPCR) which is bound to the G protein with alpha i unit, it inhibits the amplifier enzyme adenylyl cyclase.
- this means ATP doesn’t make cyclic amp and no protein kinase As are activated for a cellular response
