Ch. 16 Principles of Cell Signaling Flashcards
list ways cells can respond to their environments
- cell movement
- shape
- metabolism
- gene expression
what is the purpose of cellular communication, particularly for multicellular organisms
- reflexes
- behaviours
- development
- survival
briefly describe the pathway of cells sending signals
signal cell sends signal molecules which binds to extracellular receptor on target cell and creates a response
list the stages of cell signaling
- reception
- transduction
- response
describe the reception stage of cell signalling
- target cells sense signal molecule is coming their way
- signal molecule (=ligand) binds to cellular receptor protein either on or inside cell
describe the transduction stage of cell signaling
- binding causes conformational shape change for activation
- signal is converted into a form that will generate a response –> multiple = signal transduction pathway by relay molecules
describe response stage of cell signaling
- cellular activity results from transduced signal (i.e. catalysis, rearrangement of cytoskeleton, gene activation)
draw out endocrine signaling
- main point: thru bloodstream
draw out paracrine signaling
main point: direct & close
draw out neuronal signaling
main point: NT, axon, synapse present
draw out contact-dependent signaling
main point: membrane-bound signal molecule attaches onto receptor of target cell
cell specialization is an important mechanism for many organisms. how does it work? use fruit flies as ex.
- multicellular organisms don’t need to rely on one cell for survival which allows the cells to have same general properties but differentiate in roles
- in fruit flies one cell in centre of unspecified epithelial cells will turn into a neuron
- the cells around the neurons will differentiate into non-neuronal cells
how do cells decide what signals to respond to
dynamic receptor protein expression (few receptors to begin with, some of these inactivate, internalize, degrade, etc.)
draw out response of heart muscle, salivary gland, and skeletal muscle cells due to their signal molecules
main points: hmc = lower heart rate and force of contraction
sgc = secretion
smc = contraction
a cell’s response to a signal can be fast or slow. how can we immediately know is the response is slow
when transcription/translation needed
draw out the flow for main steps in fast and slow cell response to signal
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draw out the dif b/w cell surface and intracellular receptors
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steroid hormones are able to activate gene transcription. draw out this slow pathway showing steroid hormone outside cell reaching nucleus with main steps
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what are the main classes of cell-surface receptors
- ion channel-coupled
- G-protein coupled
- enzyme-coupled
some intracellular signaling proteins are able to act as molecular switches (can turn ON/OFF). draw the cycles of how signaling by protein phosphorylation and by GTP-binding protein can occur
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describe intracellular signaling pathways of extracelullar signals. draw out the pathway with main steps
- simple path to target
- has amplification step to inc response efficacy
- signal can be distributed to dif target pathways
describe GPCRs
- biggest family of cell surface receptors
- evolutionarily ancient
- similar core structures
- different functions
- membrane associated
- activators for G proteins
what are the subunits for G proteins
α, β, γ
draw out how GPCRs activate G proteins
main points: resting state with GDP; receptor activates with signal molecule and GDP dissociation; GTP binds to α for effector activation
draw out how target proteins are activated by G proteins
main points: GTP x α bound activated subunit attaches to target protein which causes GTP hydrolysis into GDP +P
inactive α subunit attaches to activated β γ complex making inactive G protein
why are on/off molecular swtiches important
- don’t always want a response
- EX no off switch w cholera toxin leads to diarrhea and cause cause death in extreme situations
draw out how heart rate regulation occurs with G proteins and K+ channels
main points: acetylcholine binds to GPCR activating K+ channel
K+ exits and G protein inactivates by hydrolysis which makes channel close
inactive α subunit attaches to activated β γ complex making inactive G protein
what type of effect does K+ have on heart muscle
- inhibitory
- prevents heart from contracting as fast
adenylyl cyclase is able to catalyze
cAMP synthesis
phospholipase C (PLC) is able to catalyze
IP3 and DAG synthesis
how can Ca+2 be an important intracellular messenger
- neurotransmission
- contraction
- secretion
- fertilization
draw out how G protein activation leads to phospholipase c activation and further leads to IP3 and DAG synthesis
main points: signal molecule activates GPCR; activated g protein leads to activated phos. lip. c making inositol phospholipid; this splits into DAG (diaglycerol) and IP3. IP3 opens Ca+2 channel to let Ca+2 ions from ER lumen go to (cytosol) PKC and DAG also attaches to PKC causing activation
how is Ca+2 able to mediate cell responses
Ca+2 entering the cytosol is able to interact with Ca+2 responsive proteins
what is the most common Ca+2 responsive protein
calmodulin (main intracellular receptor)
how does Ca+2 affect calmodulin
- binding leads to conformational shape change
- calmodulin wraps around the target protein/kinase and causes activation
- an example of this is calmodulin-dependent protein kinases which cannot activate
what is the largest class of enzyme-coupled receptors
receptor tyrosine kinases (RTKs)
what are enzyme-coupled receptors
- single transmembrane proteins with extracellular ligand binding domain
- have enzymatic activity themselves
what are intracellular domains capable of acting; doing
- enzyme;
- forming a complex with another protein that acts as an enzyme
define dimerization
two signal molecules that are able to bring 2 receptors together through bonding
draw out how RTKS are activated by dimerization
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what does RTK activation by dimerization
complex of proteins bound to phosphorylated tyrosines
why are phosphates important in activation of downstream intracellular signaling pathways
phosphates are able to recruit proteins that propagate signals further
most RTKs are able to activate the what protein
monomeric GTP-binding protein Ras
describe the Ras protein
- molecular switch
- intrinsic GTPase activity
draw out how Ras is able to be activated
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what results can activation of MAP-kinase signaling molecules lead to
changes in protein activity and gene expression
what happens if the Ras protein has a mutation
- mutation interferes w/ GTPase activity, which prevents Ras from turning off (~30% of human cancers)
- GTP cannot hydrolyze