Toxicant Effects on Signal Transduction Flashcards
general principles of signal transduction
cell-cell signaling is an essential characteristic of eukaryotic cells it coordinates growth, differentiation, metabolism of cells
signaling through extracellular mediator examples:
endocrine paracrine (what nerves do) autocrine (self-reinforcement, happens often during development)
signaling through cell-cell contact examples:
gap junctions
process of signal generation and delivery
ligand -> receptor -> intermediate events -> response
intermediate events of extracellular signaling
GTPase switches, second messengers, adapters, protein kinases, transcription factors
Signal generation - hydrophilic signals are
synthesized and stored in secretory vesicles
secretion is often regulated by calcium
Signal generation - hydrophobic signals are
typically released as soon as they are generated
the half-life of a hydrophobic signal determines a chronic, endocrine response or a transient paracrine response
exocytotic release; what hypothesis is used?
the SNARE hypothesis
SNARE’s are
integral membrane proteins that are found on both the vesicles and the target membranes
v & t SNARES form a high-affinity complex that contributes to
vesicle docking fusion
the docking process is regulated by the
small GTPase Rab3A
the fusion process is regulated by
calcium binding proteins like synaptotagmin
increase in intracellular calcium triggers what??
fusion of vesicles with the plasma membrane which results in releasing of neurotransmitter into synpatic cleft
how does a cell convert stimuli into response?
acute and chronic signaling
acute response
modification of already existing enzymes in the target cells
primary effect of ligands that bind to cell surface receptors
chronic response
alteration of pattern of gene expression
primary effect of ligands that bind to intracellular receptors
common later effect of ligands that bind to cell surface receptors
3 major classes of cell surface receptors
- ion channel coupled
- GPCR
- enzyme coupled
voltage-gated ion channels
are on the plasma membrane of all electrically excitable cells
GPCR’s
-have 7 transmembrane spanning alpha-helicies with their N terminus extracellular and their C terminus intracellular
GPCR binding
ligand -> receptor -> G protein -> effector
what is the effector with GPCRs?
its an ion channel or an enzyme that generates a second messenger
Examples of GPCR
morphine, ergot, atropine, cocaine
covalent modification can
direct location, activity or interactions of proteins with others
acute effects mediated by kinases
activation/inhibition of enzymes
chronic effects of kinases
activation/inhibiton of transcription factors