-promote or inhibit what?
-what is the response element?
-promote or inhibit the recruitment of RNA polymerase to specific genes
-defining feature is the presence of the DNA-binding domain
-response element is the specific DNA sequence the TF binds to
acetylcholine, epinephrine, norepinephrine, dopamine, serotonin, histamine
adrenocorticotropin, angiotensin, bradykinin, opioids
leukotrienes, prostacyclin, TxA2
adenosine, ADP, ATP
Structure of GPCR:
-N terminal domain (extracellular) often is what?
-C-terminal domain (cytosolic) contains multiple what?
-cytoplasmic loops contain?
-7 TM domain formed by a single polypeptide chain
-N-terminal domain is often glycosylated
-C-terminal domain contains multiple phosphorylation sites (serine/threonine residues)
-cytoplasmic loops contain G-protein binding sites
1. basal unstimulated state
2. Agonist activates receptor
3. which promotes release of GDP from the G Protein
4. Allows entry of GTP into nucleotide binding site
5. Signal terminated by hydrolysis of GTP
6. Return of system to (1)
Classification of G-protein families based on what?
based on Ga subunit-induced effects
Gs Gi Gq
-effect on adenylyl cyclase and Src tyrosine kinase
Gs activates all isoforms of adenylyl cyclase and Src tyrosine kinase
Gi inhibits adenylyl cyclases but activates tyrosine kinase Src
Gq activates phospholipase Cß
cAMP second messenger pathway
Ca2+-phosphoinositide signaling pathway
Receptors w/ Intrinsic Enzyme Activity:
IGF-1, Insulin, VEGF, EGF, NGF, PDGF
Structure of RTKs
-exception to general rule
most RTKs possess a single polypeptide chain, but insulin and IGF receptors have 2 chains, alpha and beta, linked by a disulfide bond
-ligand-binding shows very little similarity between members of the family, but the tyrosine kinase domain is similar
Mechanism of activation of the epidermal growth factor receptor:
-what happens upon binding?
-what happens when cytoplasmic domain becomes phosphorylated?
-upon binding of EGF (circle), the receptor converts from its inactive monomeric state (left) to an active dimeric state (right), in which two receptor polypeptides bind noncovalently.
-the cytoplasmic domains become phosphorylated (P) on specific tyrosine residues (Y), and their enxymatic activities are activated, catalyzing phosphorylation of substrate proteins (S)
-what kind of RTK?
-transmits the effect of which hormones/cytokines? (x5)
-it is a receptor coupled to cytosolic protein kinases
-transmits GH (somatotropin), Erythropoeietin, Leptin, Interferons, Interleukins 2 through 10, 15
come back to this one
ligands: four examples
ligands are lipophilic molecules that can cross cell membrane
-examples include: steroids, thyroids, Vit D,A, and Lipid mediators such as FFAs and their products
-persistence of effects?
produce their effects after a lag period, effects can persist after the agonist concentration has been reduced to zero
Mechanism of steroid hormone action:
-how many domains does nuclear receptor polypeptide have?
-hsp90 binds to what?
-binding of a hormone causes?
-hsp90 binds to the receptor in the absence of hormone and prevents folding into the active conformation of the receptor
-binding of a hormone (steroid) causes dissociation of the hsp90 stabilizer and permits conversion to the active configuration
Voltage gated sodium channels:
-drug examples that inhibit these channels
-composed of alpha and beta subunits
-examples of drugs include local anesthetics, antiarrhythmic drugs, drugs used for epilepsy treatment
voltage gated Ca2+ channels
-where are L type channels located?
-targets of what kind of drugs
located on cardiac and smooth muscle cells, targets of widely used drugs, calcium channel blockers or calcium antagonists (verapamil)
Direct Ligand-Gated Ion Channels:
-excitatory vs inhibitory
they are receptors for NTs that have an ion-conducting pore
Excitatory NTs open cation channels (ACH, Glutamate)
Inhibitory NTs open anion channels (GABA, Glycine)
Nicotinic Acetylcholine receptors:
-activation causes what?
-structure and location
-activation induces inward sodium influx and membrane depolarization
-petameric receptors with two major locations: skeletal muscle and neuronal cells
-cause inward flux of what?
- GABAmediates synaptic inhibition where?
-Anionic channels causing inward Cl- influx and hyperpolarization
-mediate synpatic inhibition in CNS via these channels
-target for inhalation GA drugs, IV GA drugs, Ethanol, Hypnotic/anti-anxiety benzos