Test 3: Lecture 55 Flashcards
plasma membrane hormone receptors are for ___ hormones
amino acid derived
intracellular hormone receptors are for ___ hormones
steroid
all protein derived hormones bind plasma membrane of the target cell but do not ___
enter the target cell
Three classes of plasma membrane bound hormone receptors
- G protein coupled receptors (GPCRs)
- Ion channel-linked receptors
- Enzyme-linked receptors
G-protein Coupled Receptors
- Common type of receptor that starts intracellular signal transduction cascades upon ligand (e.g. a hormone) binding
- Has 7 hydrophobic plasma membrane spanning domains (Serpentine Receptors)
- Hormone binding site is extracellular
- Coupled with heterotrimeric GTP binding proteins in the cytoplasm (G proteins)
___ is a common type of receptor that starts intracellular signal transduction cascades upon ligand (e.g. a hormone) binding
G protein coupled recetptors
___ has 7 hydrophobic plasma membrane spanning domains (___ Receptors)
G protein coupled receptors
Serpentine
For G protein coupled receptors the hormone binding site is ___
extracellular
G protein coupled receptors are coupled with ___ binding proteins in the cytoplasm
heterotrimeric GTP (G proteins)
Key concept of G protein coupled receptors: Ligand-induced conformational change in the receptor facilitates interactions that initiate ___ signal transduction
intracellular
changes outside will cause changes inside cell
three classes of G proteins
•Gs stimulates adenyl cyclase converting ATP to cAMP
- Gi inhibits adenyl cyclase decreasing cAMP levels
- Gq activates Phospholipase C: PIP2 >>> DAG + IP3
•Gs stimulates adenyl cyclase converting ATP to ___
cAMP
•Gi inhibits ___ decreasing cAMP levels
adenyl cyclase
•Gq activates ___: PIP2 >>> DAG + IP3
Phospholipase C
how does GPCR work
ligand binds
intracellular changes and binds to inactive heterotrimer G protein bounded to GDP
this causes GDP to break off and GTP binds and actives heterotrimer into active alpha with GTP bound
this will bind to effector protein and cause down stream activating
whole thing gets reversed to turn off
how does tyrosine kinase receptors work?
enzyme linked receptors
ligand will bind and will bring two receptors closer to each other
they will phosphorylate each other
Grb2 will bind and trigger RAS pathway
Raf→ Mek → Map
this will trigger down stream intracellular response = growth of cell
example of enzyme linked receptors
insulin receptor
example of ion channels hormone receptors
GABA receptor
amino acid derived hormone will bind and cause rate of ions through channel to increase
least common type of receptor
Binding of peptide hormones to receptors initiates a __
signal
In plasma membrane receptors for amino acid derived hormones, the signal is passed on to a ___ which typically amplifies it.
second messenger,
characteristics of second messengers of peptide hormone receptors (membrane bound receptors)
- Are small easily diffusible chemicals/intermediates
- Have very short half life
- They relay signals received at the receptors on the cell surface
- Serve to enhance the strength of the signal
- Affect more than one pathway and/ or protein
- Cause divergence of the signal
3 types of second messengers
Cyclic nucleotides (eg. cyclic AMP and cyclic GMP)
Phospholipid derivatives (eg. Diacyl glycerol, Inositol triphosphate)
Ions (eg. Ca2+)
second messengers help increase signal from membrane bound receptors for protein derived hormones
how does cAMP work as a second messenger
cAMP will bind to R which is attached to inactive PKA (protein kinase A)
R will let go of PKA and will activate PKA
active PKA can then lead to gene expression
why have second messanger system
will greatly enhance the signal.
1→ many very quickly
phospholipid derivative second messanger
phospholipase C will cut PIP into DAG and IP3
DAG will activate calcium channels in the cell membrane. influx of calcium will act as additional second messanger
IP3 will active intracellular Ca channels
•Ultimately, second messengers and downstream signal transducers activate, repress, or modulate ___ programs
gene expression
Signal transduction activates ___
transcription factors
___ is the main way that cells generate a response to hormone binding. (Though not the only way – some signals stay in the cytoplasm)
second messanger (membrane bound receptors for amino acid derived hormones)
•Gene expression programs are executed by ___
transcription factors
example of nuclear hormone receptors
used for steroid hormones
glucocorticoid receptor (21 carbon steroid hormone produced by adrenal cortex in response to stress)
GR lives in cytoplasm, ligand (cortisol) comes into cell and binds and triggers GR to move to nucleus and causes gene expression
how does GR move to nucleus
- GR is held in cytoplasm by heat shock protein complexes
- Intracellular ligand binding (eg. cortisol) induces conformational change that frees GR from heat shock protein complex
- Nuclear localization signal on GR induces translocation to nucleus
will bind to GRE in the nucleus act as transcription factor
nuclear receptors are used for ___ hormones
steroid
•GR is expressed ___in most tissues
ubiquitiously
•There are the same number of GR DNA binding motifs in the same genomic locations in ___, Yet GR activation has different ___ in different tissues.
all cells
effects
motif are different inside DNA. (DNA might be the same but it is wound or open in different spots- epigenome is different between cells)
