Biosignaling-German Flashcards
What are the requirements for effective signal transduction
specificity, amplification, modularity, integration, feedback, fidelity
define specificity
receptors/proteins bind specific ligands/substrates
define amplification
small signal will lead to large effects
define modularity
different components of
define integration
all signals in context tell a cell what to do
define feedback
tool for which a pathway is turned off or on
fidelity
transport of input without losing the signal, maintenance of signals
intracellular signaling
within a single cell
intercellular signaling
between two or more cells
4 types of intercellular signaling
autocrine, paracrine, synaptic, endocrine
define autocrine signaling
1)shortest distance, immediate signaling, right there, type of intercellular signaling
define synaptic signaling
2)short distance, signals sent very small distances (less than a micron, 70-90 nm), type of intercellular signaling
define paracrine signaling
3)medium distance, signal released to induce cells in its immediate environment, signals its neighbors, type of intercellular signaling
define endocrine signaling
4)long distance signaling, goes into the vasculature, type of intercellular signaling
Four components of signal transduction
signal, receptor, transduction pathways, targets
what is the primary excitatory transmitter(?) of the nervous system?
glutamate
Types of signals
soluble, linked, physical
types of soluble signals
proteins & amino acids, lipids & FA’s, Carbohydrates
types of linked signals
integrin
types of physical signals
mechanical (mechanoreceptors), light (opsin), temperature (TRP Channels)
Name the receptor families
1) g-protein coupled, 2) receptor tyrosine kinase, 3) receptor guanylyl cyclase, 4) ligand gated ion channels, 5) adhesion, 6) nuclear, and 7) cytokine
g-protein coupled receptors
metabotropic, bind soluble ligands, external ligand (L) binding to receptor (R)
Receptor tyrosine kinase
metabotropic, bind soluble ligands
receptor guanylyl cyclase
metabotropic, bind soluble ligands
ligand gated ion channel
bind soluble ligands
adhesion receptors
metabotropic, ..
nuclear receptors
.metabotropic,
cytokine receptors
metabotropic
cytokine receptor families
interleukin type I, interleukin II, TNFR (tumor necrosis factor receptor), and Ig families
define Kd
the point at which you reach half-maximum of binding,
the amount of ligand concentration you need for half the lingands(?)/binding sites(?) to be bound
define the plasma membrane’s active roles in signaling
receptor localization, ligand exposure, signaling complex formation, endocytosis
define receptor localization in signaling
/
define ligand exposure in signaling
.
define signaling complex formation in signaling
1)protein scaffolds:, 2)signaling endosomes: protein scaffold internalized within endosome —> creates dramatically smaller volume than whole cell –> dramatically increases ligand binding due to increased concentration (one way cells maintain fidelity)
define endocytosis in signaling
.
types of lipid rafts
caveolar and planar, can promote or inhibit signals
caveolar lipid rafts
envagination, increase liklihood of ligand binding receptor
what type of endocytosis does not require a lipid raft?
clathrin-mediated endocytosis
what types of endocytosis occur in mixed membrane domains?
phagocytosis and macropinocytosis
what happens to the pH as you move along the endocytic pathway?
it decreases
define the three way signals are altered by the endocytic pathway
signal cessation, signal amplification, and signal initiation
define signal cessation
signal downregulation,
define signal amplication
signal maintenance, help maintain signal fidelity,
define signal initiation,
signal generation, signal doesn’t become active until it reaches the receptor
first messenger
the initiating ligand [ex. neurotransmitter] that activates its receptor
receptor
has a signal transducer [ex. metabotropic NT receptor]
signal transducer
will activate primary effector [ex g-protein] (receptor tyrosine kinases and guanylyl cyclase skip this step/they don’t have a signal transducer)
primary effector
[ex. adenylyl cyclase]
second messenger
activated by primary effector, activates secondary effector [ex. cyclic AMP]
secondary effector
enzyme [ex. protein kinase A]
signaling cascade
don’t necessarily need to start with secondary effector (can start earlier in signal transduction pathway/skip steps)
Through what methods do chemical rxn’s transfer information
complex formation or dissociation, structural change, post-translational modifications
List the prevalent post-translational modifications
phosphorylation, ubiquitination, glycosylation, oxidation, methylation, acetylation, SUMOylation (change structure to facilitate interaction later down the line)
List the common signaling cascades
1) Mitogen-activated Protein Kinase [MAPK], 2) Janus Kinase-signal transducer and activator of transcription [JAK-STAT], 3) Phosphatidylinositol 3-kinase [PI3K], 4) Phospholipase C [PLC]
mitogen-activated protein kinase (MAPK) signaling
start with activated RAS–>activates MAP kinase kinase kinase–>phoshorylates MAP kinase kinase–>activates MAP kinase
JAK-STAT Signaling
JAK in pairs–>phosphorylate cytoplasminc receptor tail–>recruits STAT proteins–> (the most direct and fastest signaling pathway for generating…)
PI3K Signaling
phosphatid….
start to interact with lipids
phosphorylate PIP2–>turns into PIP3–>interact with PDK1 and AKT–>interacts with mTORC1
know that PIP2 and PIP3 activate PDK1 and AKT which interact with
Phospholipase C Signaling
breaks apart lipids
PIP2–>cleaved to become IP3 and DAG–>IP3 interacts w/ receptors that release 2nd messenger Ca
DAG–>
List the targets of cellular signals
Nucleus, actin/tubulin/filaments, enzymes, receptors, transporters, ion channels
What change in cellular function occurs upon nucleus signaling
transcription, cell division
What change in cellular function occurs upon actin/tubulin/filament signaling
cell structure and motility
What change in cellular function occurs upon enzyme signaling
intitiate metabolic pathways
What change in cellular function occurs upon receptor signaling
alter signal transduction
What change in cellular function occurs upon transporter signaling
change intracellular environment
What change in cellular function occurs upon ion channel signaling
change membrane potential
relevant signaling pathways
1) epinephrine signaling and 2) insulin signaling
Epinephrine signaling
- affects vascular tone
- co-administered with local anethetics
- g-protein and PLC signaling
insuling signaling
-
epinephrine affecting vascular tone
epinephrine binds B-adrenergic receptor: - higher concentrations: -you get norepinephrine and epinephrine -
at lower concentrations of epinephrine, epinephrine binds to____. What is the physiological effect?
will predominantly bind to B-adrenergic receptors
vasodilation
at higher concentrations of epinephrine, epinephrine binds to____. What is the physiological effect?
will bind more to alpha-adrenergic receptors
vasoconstriction
insulin signaling pathway
insulin receptor binds insulin –> autophosphorylation of tyr residues –> tyr residues phosphorylate IRS-1 –> its P binds Grb2 –> binds Sos –> binds Ras –> release of GDP from Ras and binding of GTP to Ras –> Activated Ras binds and activates Raf-1 [MAPK3] (1st step of MAPK pathway) –> phosphorylates/activates MEK [MAPK2] –> phosphorylates/activates ERK [MAPK] –> ERK enters nucleus and phosphorylates/activates TF’s –> stimulates transcription/translation –> cell division, cell growth, protein production, etc…
define the meaning of a low Kd
higher affinity for that ligand at that concentration
define the meaning of a high Kd
lower affinity for that ligand at that concentration
