Biosignaling Flashcards
what are the 6 requirements for effective signal transduction?
specificity, modularity, amplification, integration, feedback, and fidelity
describe how specificity is important for effective signal transduction
receptor must have specificity for a particular signal
describe how amplification is important for effective signal transduction
a signal will activate an enzyme, which will then produce signaling molecules to activate more enzymes, which will then also produce signaling molecules to activate even more enzymes
describe how modularity is important for effective signal transduction
- a signal has a very discreet pathway of initiation at the receptor to a specific target
- this is important because the target is dynamic and can respond to different signals
describe how integration is important for effective signal transduction
multiple signals for multiple receptors are summated to come up with one ultimate response
describe how feedback is important for effective signal transduction
helps regulate signals by either turning them down or amplifying them
describe how fidelity is important for effective signal transduction
- a signal is initiated from a molecule at the plasma membrane and must reach its target at a different location
- fidelity describes the ability of the signal to resist change before reaching its target location
describe autocrine signaling
- self-stimulating, local response
- cell releases inducer molecule and causes a response in itself
describe synaptic signaling
- synapses are seen in both the nervous system and immune system
- signals are restricted to a defined area
- small scale local signaling
describe paracrine signaling
- occurs in exracellular space in an environment within a few microns of the signal initiation
- communication between organ systems
- signals are not restricted to a specific organ type, but they are restricted to a specific area
describe endocrine signaling
- largest domain of signaling
- signal released into the vasculature or lymphatic system and will travel to various areas of the body
- insulin and epinephrine are examples
what are the 4 components of signal transduction?
- signal
- receptor
- transduction pathways (ex. STAT and MAPK)
- targets
what are 3 main types of signals?
- soluble - proteins and amino acids, lipids and fatty acids, and CHOs
- linked
- physical - mechanical, light, and temperature
what are examples of soluble signals?
- proteins and amino acids: epidermal growth factor
- lipids and fatty acids: ceramide and testosterone
- carbohydrates: glucose
what is an example of a linked signal?
integrin
what are examples of physical signals?
- mechanical: mechanoreceptors
- light: opsin
- temperature: TRP channels
name the 7 canonical receptor families
- G-protein coupled receptor
- receptor tyrosine kinase
- receptor guanylyl cyclase
- ligand gated ion channel
- adhesion receptor (integrin)
- nuclear
- cytokine
name the 4 cytokine receptor families
- interleukin type I family
- interleukin type II family
- TNFR
- Ig family
describe G-protein coupled receptors
- external ligand binds to receptor
- activates intracellular GTP binding protein
- GTP binding protein regulates enzyme that generates an intracellular second messenger
descbie receptor tyrosin kinases
- ligand binding activates tyrosine kinase activity by autophosphorylation
- kinase activates transcription factor, altering gene expression
describe receptor guanylyl cyclases
- ligand binds to extracellular domain
- stimulates formation of second messenger cyclic GMP
describe ligand gated ion channels
- opens or closes in response to concentration of signal ligand or membrane potential
describe adhesion receptors
- binds molecules in extracellular matrix
- undergoes conformational change
- interaction with cytoskeleton is altered
what is Kd?
- the dissociation constant, which describes the concentration of ligand required to occupy one half of the total available receptors
- calculated as [L][R]/[LR]
- L = ligand
- R = receptor
- ligand concentration dramatically impacts signaling
which 4 major roles does the plasma membrane play in signaling?
- receptor localization
- ligand exposure
- signaling complex formation
- endocytosis
describe how protein scaffolds form signaling complexes
- protein scaffolds bring all signaling components together along the plasma membrane, forming a signaling complex
describe how signaling endosomes form signaling complexes
- a signal induces activation of a receptor, and that whole complex along with all signals is internalized into an endosome
- that endosome then travels to its target
how do lipid rafts affect signal activation and progression?
- they pull together different signaling components in unique places on the plasma membrane
- this influences signal activation by either keeping the right components together to increase signal activation, or by moving certain components out to prevent signal activation
- signal promotion vs signal inhibition
describe the 2 types of lipid rafts
- caveolar: lead to caveolar mediated endocytosis; can artificially increase binding of ligand to receptor by trapping it in the lipid raft and increasing [L]
- planar: continuous with the plasma membrane
describe the sorting of internalized vesicles via the endocytic pathway
- endocytosis creates a vesicle, which fuses with the early endosome
- signals are then sorted and sent to their specific locations within the cell
- presence or absence of different Rab GTPase proteins guides vesicles to specific locations
- two ultimate fates of the signals: (1) degradation in the lysosome, or (2) recycling endosome moves signals back to plasma membrane
T or F:
pH increases along the endocytic pathway
false:
pH decreases along pathway
describe how the endocytic pathway spacially and temporally regulates signaling
- signal downregulation
- signal maintenance
- signal generation
describe the steps of signal transduction from first messenger to signaling cascade, and name the components in each step
effectors are usually enzymes
describe how chemical reactions transfer information
- can cause structural changes of enzymes or signals, post-translational modifications, or complex formation or dissociation
name the 7 prevalent post-translational modifications
- phosphorylation (adds phosphate group)
- ubiquitination (adds ubiquitin)
- glycosylation (adds glycan)
- oxidation (loss of H)
- methylation (adds methyl group)
- acetylation (adds acetyl group)
- SUMOylation (adds SUMO protein)
name the 4 common signaling cascades
- mitogen-activated protein kinase (MAPK)
- janus kinase - signal transducer and activator of transcription (JAK-STAT)
- phosphatidylinositol 3-kinase (PI3K)
- phospholipase C (PLC)
describe characteristics of signaling cascades
- receptors activate multiple signaling cascades
- conserved signal transduction process
- variable messengers
- signals are context specific
describe the steps in MAPK signaling
- GTP (activated RAS) activates MAPKKK
- phosphorylation (ATP -> ADP)
- MAPKK activated
- phosphorylation (ATP -> ADP)
- MAPK activated
- targets are phosphorylated
describe the steps in JAK-STAT signaling
simplest signal transduction pathway, so there is not much room for modification
- receptor dimerizes and recruits JAK protein
- phosphorylation of tail of receptor, causing recruitment of STAT protein to tail
- JAK phosphorylates STAT protein
- STAT protein dimerizes and moves to nucleus
describe the steps in the PI3K signaling pathway
*PI3K phosphorylates a lipid, not an enzyme*
- PI3K phosphorylates PIP2 to PIP3 (these lipids are bound to the plasma membrane)
- PIP3 activates PDK1 and AKT
*AKT inhibits its targets and can prevent protein synthesis, cell cycle, and cell survival
describe the steps of phospholipase C signaling
- phospholipase C activated by G-protein coupled receptors
- activated phos. C cleaves PIP2 into IP3 and DAG which remains in the plasma membrane
- IP3 interacts with ER/SR and causes release of calcium
- Ca2+ activates PKC, which then interacts with DAG on the plasma membrane
- PKC can then phosphorylate other substrates
what is crosstalk?
products of different pathways “talk” to each other and influence each other
describe the 6 main targets of signal transduction and how they are affected
- nucleus: transcription, cell division
- actin/tubulin/filaments: cell structure and motility
- enzymes: initiate metabolic pathways
- receptors: alter signal transduction
- transporters: change intracellular environment
- ion channels: change membrane potential
describe the epinephrine signaling pathway
- affects vascular tone
- co-administered with local anesthetics
- utilizes G-protein coupled receptors and PLC signaling
two pathways:
- epinephrine interacts with beta adrenergic receptors; result is formation of cAMP from ATP, causing smooth muscle relaxation and vasodilation
- epinephrine interacts with alpha adrenergic receptors; activates PKC alpha and calcium-calmodulin complex, causing smooth muscle contraction and vasoconstriction
describe the insulin signaling pathway
- regulates cellular division and metabolic processes
- transports glucose into cells, alters blood sugar, enables aerobic respiration
- utilizes RTK, MAPK, and PI3K signaling
