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23 Cards in this Set
- Front
- Back
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describe intracellular steroid receptors
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receptors for small, hydrophobic molecukes, ligand activated transcription factors
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what are the three domains of a steroid hormone receptor
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1. hormone binding 2. DNA binding 3. transcription activating
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describe the mechanism of signaling by steroids
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Hormone is released from BP and dissues through PM to receptor which activators a conformational change. This change releases the complex form inhibitory proteins and allows it to bind with high affinity to the HRE near the promoter of the target gene=modulation of transcription of a small number of genes
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Describe the nicotinic ach repceptor
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cation selective, excitatory, found on NMJ, PNS, CNS, converts Ach binding into electrical signal in the post-synaptic cell
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describe the GABA receptor
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CL- channel, inibitory
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What are the functions of Gas, Gai and Gaq
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Gas=stimulates AC= more cAMP, Gai=inhibits AC, less cAMP, Gaq=stimulates PLC=IP3, DAG
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How are heterotrimeric G proteins activated
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binding of the ligand to the GPCR stimulates the exchange of GDP for GTP. Binding of GTP to the alpha subunit leads to dissociation of the trimeric complex allowing the Ga-GTP to inteact with effectors
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describe the structure of tyrosine kinase linked receptors
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single protein with one transmembrane domain which dimerizes upon ligand binding (or dimer=>tetramer), cytoplasmic domain has tyrosine specific protein kinase activity, binding of ligan leds to cross-phosphor
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what is the function of DAG
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made when PLC cleaves PIP2, DAG remains in the cell membrane and actiates PKC
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what is the function of IP3=
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made when PLC cleaves PIP2, binds to receptors on ER leading to calcium release
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describe the GCPR/Gas/cAMPpathway
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ligand binds GPCR which leads to exchange of GDP for GTP on the Gas. Active Gas then activates AC which makes cAMP. cAMP activates PKA, PKA phosphorylates other proteins e.g. CREB, p-CREB binds DNA and induces gene transcrption
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Describe the GPCR-inositiol-lipid pathway
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Ligand binds GPCR and causes excahnge of GDP for GTP on Gaq. Gaq-GTP actiats PLC. PLC cleves PIP2=>IP3, DAG. DAG stays in the membrane and activates PKC (with Ca), IP3 difuses to the ER and releases Ca, Ca binds to calmodulin and activates Ca/calmodulin dependent protein kinase
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How are monomeric G proteins activated and inactivated
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Activated when a GEF causes release of GDP and binding of GTP. Inactibated when a GAP induces the monmeric G protein to hydrolyze the GTP to GDP
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Describe the Map Kinase pathway
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Ligand binds tyrosine kinase receptor, cross phosphorylation allows for the docking of the adaptor protein and recruitment of SOS (a GEF), Ras (a monomeric G protein) binds SOS and exchanged GDP for GTP. Ras-GTP goes on to activate the MAP kianse cascade (MAPKKK (Raf), MAPKK (MKK1), MAPK (ERK), ERK phsophorylates many TF's
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activating mutations in the EGF receptor or RAS can lead to tumors because of abnormally high activity in the pathway. Name two drugs that inhibit the siganling of the EGF receptor. How do they work?
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gefitinib, erlotinib, inhibit the kinase domain of the EGF receptor, only effective in pts who have tumors with mutated EGF receptors
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Receptor mediated endocytosis is an eample of adapatation. How does this work
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Upon binding of ligans, receptors migrated to coated pits and are endocytosed, the vescile fuses with CURL and the complex dissociates. Most of the ligand incorporates into the vesicle which fuse with lysosomes. The receptors can recirculate to the cell membrane are sequestered or are degraded. Note that the internalized ligand never enters the cytoplasm
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What is the difference between homologous and heterlogous desensitization
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homolougs-only the stimulated receptor is attenuated, heterlogos-both stimulated and unstimulated receptors are attenuated
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Exaplin how the Bark/ b arrestin system results in homologous receptor desensitization
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BARK phosphorylates the active GPCR which allows for binding of b-arrestin, this turns off the receptor
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How might heterologous desensitization occur
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covalent modification, competition for shared second messengers
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what does GEF stand for
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guanine nucelotide exchange factor
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what does GAP stand for
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GTPase activating protein
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what is raf
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a MAP KKK
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what is ERK
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a MAP kinase
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