Mechanisms of Cell Signalling Flashcards
Response types and examples
Reversble-become motile/change shape
Irreversible-divide, differentiate/remain undifferentiated, die
Cells sense environment bye
Specialized receptor proteins
Ligands+specificity
Molecule that triggers signal by binding to receptor
-specificity governed by tertiary structure and non-covalent bonds between AA groups
Agonists vs antagonists
agaonists-induce receptor activation
-occupies ligand binding site and stimulates receptor activity
antagonists-block receptor activation
-occpies ligand binding sites and exclusde agonists /change conformation of receptor
where do drugs act
either receptors or enzymes
Ion channels
Pore forming protein that allow flow of ions across membranes down electrochemical gradient
Ligand gated channel
Bind ligand to open channel to allow flow of ion across membrane-or close to slop flow
Basis for nerve transmission and muscle contraction
Channels are oligomeric (can form groups that do not let anything through)
CFTR
Cystic fibrosis transmembrane conductance regulator
- recessive disease-loss of function mutation
- abnormal salt transport-mucous buildup
- ligand=ATP
GOF mutations to ion channels
Domnant inheritance-create defects in other ion channels b/c oligomeric bonding
-only 1 bad receptor fucks up others
Mutations in voltage=dependnent Na” channels
GOF
Results in defective inactivation and late Na+ currents
Tetrodotoxin
Pufferfish toxin
-Na+ channel blocker-blocks action potentials in nerves
Nucelar Steroid hormone receptors
Derived from cholestorl-control gene expression
Hydrophobic hormones-cross cell membrane
Bind to receptors in cyto or nuc
Chaperone may help prior to ligand binding
Estrogen
Enter cell, binds to chaperone, binds to receptor, receptor causes estrogen dissociation from chaperone and exposes nuclear import signal=homodimerizaiotn and nuclear entry occur
Bind to ERE (dna promoter) to activate gene trx
Estrogen receptors are overexposed in breast cancer cells
Endocrine therapy for breast cancer
Use selective estrogen receptor antagonists-tamoxifen
Protein Kinase receptors Pathway
Ligand binds to extra cellular domain
Subunits dimerize-cytosolic protein kinase domains are now in proximity
Kinases phosphorylate each other (usually multible P’s)
Additional cytosolic proteins recruited to receptors (bind to phosphorylated tails)
Phosphorylation
Reversible
On/Off switch
Can turn hydrophobic portion of a protein into hydrophilic
Conformational change-facilaitate interaction
Grb
G-protein receptor binding
Binds to phosphylated g receptors
Constains SH2-doman that recognizes phosphorylated kinase (tyr-P)
Tyr-P
AA that gets phosphorylated in protein receptor kinase cascade
SoS
GEF=son of sevens
-bnds to grb and activates small G-prtoeins such as Ras
Ras
Monomeric small g=protein, activated by SoS
GEFs
Guanine nucleotdie exchange factors
Activate G proteins (like RAS) by catalyzing exchange of GDP for GTP
GAPs
GTPase activating proteins
Promote inactivation o G prpteins by cleaving phosphate group from GTP to make GDP
G-proteins
Bind guanine nucleotides and act as molecular switch during signalling
DRAW-NUCLEOTIDE EXCHANGE REACTION AND G PROTEIN=SLIDE 30
SoS recruited to actiate protein kinase receptor-induce exchange of GDP for GTP on Ras
- Ras is inactive with GDP bound
- SoS is ras GEF
- Ras is now activated-weak gap function, hydrolyzes GTP to GDP slowly (weak gap function) there is also gap proteins that push process along wit proper timing to allow inactivation of as from GTP to GDP
- intrinisic and other proteins push along GTP to GDP
