Cell Signaling and Signal Transduction- Exam 1 Flashcards
Cell theory
- living organisms are made of cells
- cells are the building blocks of life
- all existing cells come from pre-existing cells
Signal input for cells
physical environment and other cells
Signal output from cells
extracellular matrix and signals to other cells
What do signal transduction pathways do?
regulate transcription factor and other cytosolic metabolic pathways directly
Types of signaling
- direct
2. indirect
Direct signaling
signals pass through gap junctions which are made of six connexin proteins, this way small molecules can pass through without crossing plasms membranes. Example: calcium in glial cells
Autocrine signaling
the target cell is also the secreting cell
paracrine signaling
Signal released from a cell has an effect on neighboring cells.
hormonal signaling
a type of long-distance signaling where an endocrine excretes hormones in a blood vessel to travel to a target cell
synaptic signaling
a nerve cell releases neurotransmitter molecules into a synapse, stimulating the target cell
On and off
Phosphorylation ( on Ser. Thr. Tyr): kinases, phosphatases
G-proteins: GTP binding (activation), GTP hydrolysis (inactivation), arrestins (bind to G-protein)
Three stages of cell signaling
- Reception
- Transduction
- Response
Reception
- cytoplasmic receptors
2. transmembrane receptors
cytoplasmic receptors
signal molecules are hydrophobic and can permeate the plasma membrane, ideal for steroids such as estrogen, testosterone, and cortisol
transmembrane receptors
transmembrane proteins with extracellular binding domains that have large hydrophilic ligand binding to them and they do NOT cross the plasma membrane
- GPCRs
- Enzyme-linked receptors
- ligand-gated ion channels
GPCRs
- very common
- a frequent target for drug design (because it has amplification properties?)
- seven transmembrane helices
- three subunits: alpha, beta, gamma
- termination: initially GTP hydrolysis, then GRK/arrestins
Enzyme-linked receptors
- receptor tyrosine kinase
- only one TM segment
- ligand binding=dimerization\
- trans-autophosphorylation on tyrosine residues( what does this mean bruh?)
- termination by receptor internalization
- ligand-mediated(ligand dimer), receptor-mediated(receptor dimer)
ligand-gated ion channels
-IP3 and Ryanodine receptor (in neuro bio lecture)
Transduction
Second messengers (example: cyclic AMP)
-the first messenger is the extracellular ligand, the second messenger is its intracellular surrogate
Caffeine
Caffeine inhibits cAMP phosphodiesterase
glucose example
glucose: released from liver cells, regulated by glucagon and/or epinephrine
GPCR
effector protein: adenylyl cyclase
protein kinase A
cytoplasmic and nuclear responses
calcium example
calcium allows for buffering and hotspots and waves (e.g. glial cells)
larger concentration outside, in mitochondria, and in ER than in cytosol so when calcium is pumped into those regions an ATP powered pump is required.
activation of calcium fluxes example
GPCRs or RTKs effector protein: phospholipase C Protein kinase C second messengers: calcium, IP3, DAG
PIP2, DAG, IP3
PIP2= phosphatidyl inositol phosphate DAG= diacylgylcerol IP3= inositol triphosphate
calmodulin example
in addition to protein kinase C, sometimes calcium uses CaM to affect the downstream activity of enzymes
CaM undergoes a conformational change by binding to four calcium ions
calcium-induced calcium release in animals
what happens in brain glial cells
calcium ions can be used to release more calcium ions from the endoplasmic reticulum including from the sarcoplasmic reticulum of muscle cells
CICR in plants
when too much water is released, the hormone abscisic acid is released, this triggers the influx of calcium ions into the vacuole which causes an outflux of the calcium ions from the vacuole which then causes water to follow out of the vacuole leading to a lower turgor pressure causing the guard cells to close the pore thereby inhibiting the loss of water
amplification
cascade/amplification fo cAMP or PKA is when one ligand molecule triggers the production of infinitely more molecules downstream causing a much larger response
example: one molecule of epinephrine or glucagon can lead to the production fo 100,000 molecules of glucagon
example of amplification
RTK Ras/MAPk pathway Ras: a single subunit G-protein Ras stimulates cell division Ras is mutated in about 30% of cancers such that it cannot hydrolyze GTP to GDP which leads to continuous cell division leading to cancer due to lack of cell division termination
blood vessel dilation
- ACh receptor
- Calcium flux activates nitric oxide synthase
- nitric oxide synthase produces nitric oxide
nitric oxide activates guanylyl cyclase which leads to the production of cGMP - cGMP leads to the relaxation of blood vessels causing the blood to flow
Viagra
Viagra inhibits cGMP phosphodiesterase
Response
cytoplasmic and nuclear responses
CRE and CREB
CRE= cAMP response element CREB= CRE binding element
CREB activation in the liver
leads to the transcription and translation of genes involved in gluconeogenesis
specificity of responses
divergence: one molecule leads to two responses
crosstalk: respond to different signals and interact
example of crosstalk: PKA activates CREB phosphorylation but inhibits MAPk pathway that can also modulate CREB phosphorylation
termination of cAMP
cAMP phosphodiesterase
termination of cGMP
cGMP phosphodiesterase
termination of protein-p
phosphatase
termination of calcium ions
reuptake back into the endoplasmic reticulum or sarcoplasmic reticulum in the case of muscle cells
cholera
toxin modifies G protein so that it cannot hydrolyze GTP leading to an inability to terminate the transduction pathway leading to constant high levels of cAMP which means that the patient experiences acute diarrhea, dehydration, and vomiting
