Watts Set 3 Flashcards
what are the 5 classes of receptors
intracellular receptors
cytokine receptors
protein kinase receptors
ion channels
GPCRs
what are intracellular receptors
- Intracellular receptors (regulate gene expression) (steroids)
— Stimulate the transcription of genes
– Additional non receptor receptors
——– Effector enzymes that regulate cellular function include membrane potential, protein phosphorylation, translation, transcription, etc.
———–> Kinase, cyclase, phosphatases, ubquitinases
what are cytokine receptors
simplest
- JAK-STAT pathway
- mechanism: binds, activation leads to JAK, phosphorylation to STAT, dimerizes and travels to regulate transcription
–> Examples: GHs, erythropoietin, interferons
what are protein tyrosine kinase receptors
- Mechanism: ligands dimerize,conformational change, phosphorylation happens and recruits GRAB, leads to activation of RAS, RAS leads to transcription
—> Examples, EGF, PDGF, insulin - This pathway can be turned off by blocking
- Receptor tyrosine kinases as drug targets
—> Lots of ways to target an receptor
what are the two types of ion channels
voltage gated and ligand gated
what do voltage gated ion channels do
- No ligand just membrane potential
- Bind at allosteric sites
- In order to block we have to activate
–> Ex: na, ca,k - Involved in pain, epilepsy, arrhythmias, vascular tone, neurotransmitter release
- Channels can be regulated by phosphorylation and G proteins
what do ligand gated ion channels do
- Many drugs act by mimicking or blocking endogenous ligands that regulate flow of ions through channels
–> Ex: acetylcholine, gamma-aminobutyric acid, glutamate, etc. - When bind the signal is transmitted across membrane and alters electrical potential
- Very fast (milliseconds)
–> Important in rapid transfer of signals across synapses
what are g couples protein receptors
- Very popular in human genome and largest family
- 40% of drugs target GPCRs
- 3 classes (A,B,C)
- Ligands act by modulating effectors and concentrations of second messengers
who invented cyclic AMP in 1971
earl sutherland
what are the features of G protein activation
- effectors: channels, enzymes, regulatory proteins
- second messengers: cAMP, CA2+, phosphoinositides
what are the components of the signaling process for gpcrs
R
- extracellular ligand is detected by cell surface receptor
G
- this receptor in turn trigger activation of G protein located on cytoplasmic face of the plasma membrane
E
- activation of Galpha and Gamma/beta then changes the activity of the effector
– enzyme or ion channel
- this effector often changes the concentration of the intracellular second messengers which produce an effect
– greatly amplified response
what are the subtypes of G proteins
Gas, Gai, Gaq/11, Ga12/13, Gby
what is Gas effector
inc. adenylyl cyclase
what is Gas isoforms
gas, golf
what is Gai effectors
dec. adenylyl cyclase