Signal Transduction Flashcards
Cell Theory
- Living organisms are composed of cells
- The cell is the basic functional unit of life
- All cells arise only from other pre-existing cells
What do cells receive input signals from?
- the physical environment (light, odors)
- other cells (chemical signals)
Gap Junctions
a type of signaling where small molecules can pass readily between cells that are connected by gap junctions without crossing plasma membranes
Indirect signaling
autocrine
paracrine
endocrine (hormonal)
synaptic
autocrine
a subset of indirect cell signaling where sending and receiving cells are the same
paracrine
a subset of indirect cell signaling where the receiving cell is near the sender
ex: nitric oxide, histamine, epidermal growth factor (EGF)
endocrine (hormonal)
a subset of indirect signaling where hormones are released by the secreting cell and often travel into the circulatory system
ex: insulin, adrenaline (epinephrine), testosterone, cortisol
synaptic
a subset of indirect signaling where electrical signals stimulate the release of a neurotransmitter
ex: acetylcholine (ACh), serotonin, epinephrine, and glutamate
multiplicity of responses
the same signal can induce different responses in different target cells
ex: ACh to heart muscle > decreased rate of contraction, ACh to skeletal muscle > increased contraction, ACh to salivary glands > stimulates secretion of saliva, ACh to arteries > vasodilation
Three Stages of Cell Signaling
- Reception
- Transduction
- Response
Types of receptors
- cytoplasmic receptors
- transmembrane receptors
What are the three types of transmembrane receptors?
- G-protein coupled receptors (GPCRs)
- enzyme-linked receptors
- ligand-gated ion channels
GPCRs
- signal from outside of cell
- signal reaches G protein receptor
- G protein is activated and binds to receptor/GDP activated to GTP
- subunit of G protein attached to GTP is released and attaches to effector protein
- product and amplification
- termination by GTP hydrolysis
example: epinephrine/cAMP pathway
Epinephrine/cAMP pathway
signal = epinephrine
GPCR
effector protein = adenylyl cyclase
product = cAMP (second messenger)
enzyme-linked receptors
- only one transmembrane segment
- ligand binding leads to dimerization (ligand mediated or receptor mediated) 3. trans-autophosphorylation on tyrosine residues
- termination by receptor internalization
ex: insulin receptor
ligand-gated ion channels
include IP3 receptor, Ryanodine Receptor (RyR), and other ion channels (more in neurobiology)
Transduction
second step of cell signaling pathway and second messengers (cAMP)
Earl Sutherland’s Experiment
-intact liver cells (w/ glycogen reserves) + epinephrine > glucose release
-extract of liver cells (centrifugation) + epinephrine > glycogen converted to glucose
-cAMP = VERY IMPORTANT for breakdown of glycogen to glucose
Where are calcium concentrations high?
Endoplasmic reticulum, mitochondria, extracellular fluid
Where are calcium concentrations low?
cytosol
Transduction (amplification by cascades)
a single response can induce an even bigger response
Calcium induced calcium release
calcium ions release more calcium ions from the ER, including from specialized ER such as the sarcoplasmic reticulum of muscle cells
-based on concentration
-needs ATP to pump
ex: brain glial cells
CICR in plant guard cells
- CO2 enters leaf, water is lost
- If too much water is lost, abscisic acid (ABA) released
- ABA opens Ca channels in PM of guard cells
- Ca rushes in from cytosol and releases more calcium from vacuole
- High Ca conc. OPENS ion efflux channels in PM of guard cells that allow ions and salts to leave and CLOSES ion influx channels
- H2O follows ions and salts > reduces turgor pressure
- Stomatal pores close > ends water loss > but leaf begins to wilt b/c of water loss
What role does stomata in plants serve?
for gas exchange in the leaves of plants
-contain guard cells
turgor pressure
low = stomatal pores closed
high = stomatal pores open
cascade/amplification (cAMP/PKA)
- inactive G protein > active G protein
- inactive adenylyl cyclase > active adenylyl cyclase
- ATP to cAMP
- inactive protein kinase A > active protein kinase A
- inactive phosphorylase kinase > active phosphorlyase kinase
- inactive glycogen phosphorylase > active glycogen phosphorylase
cascade/amplification (RTK)
- growth factor (ligand)
- activates transmembrane protein
- Ras/GDP activated to Ras/GTP (stimulates cell division)
- Raf/Ras activated
- MEK phosphorylated by Ras/Raf
- MAPk phosphorylated by MEK(p)
- MAPk(p) enters nucleus and sends out cellular responses for cell to divide
transduction (blood vessel dilation)
- ACh receptor
- Calcium flux activates nitrogen oxide synthase (NOS)
- NOS converts Arg to NO
- NO diffuses to muscle cells (paracrine)
- NO activates guanylyl cyclase in muscle cells > cGMP
- cGMP relaxes muscles > increased blood flow
Nitroglycerin
metabolized to NO (helps blood flow)
Viagra and cGMP
penile isoform of cGMP phosphodiesterase is inhibited by Viagra by binding to it and maintains high levels of cGMP which allows continued dilation of blood vessels (GTP + NO + guanylyl cyclase > cGMP > maintained high levels of cGMP
Response (step 3 signal transduction) concepts
cytoplasmic and nuclear responses, specificity of responses
cAMP/PKA pathway response (cytoplasmic/nuclear)
Active PKA passes through cytoplasm and phosphorylates CREB (cAMP response element binding protein). This then binds to CRE (cAMP response element) and leads to transcription/translation of genes (in liver>genes involved in gluconeogenesis)
Definition of Specificity of Responses
Different cell types express different collections of proteins/receptors and so they can respond to different signals and/or differently to the same signals
-single response
-divergence
-cross-talk
Divergence response
pathway branches, leading to two responses
Cross-talk response
various signaling pathways have common intersecting elements and/or overlapping response processes that can lead to crosstalk/interference issues
ex: cAMP/PKA
cAMP/PKA cross-talk example
-can activate some pathways while inhibiting others
-PKA activates CREB phosphorylation (response) directly but inhibits MAP kinase pathway that can also modulate CREB phosphorylation
Termination of signal transduction pathway
Terminates signal
Termination: G-proteins
G-proteins > GTP hydrolysis (GDP) > GPCRs > GRK > arrestins > internalization
-clathrin-mediated endocytosis
Termination: cAMP/cGMP/phosphorylation
-ATP > adenyl cyclase > cAMP > cAMP phosphodiesterase > AMP
-GTP > guanylyl cyclase > cGMP > cGMP phosphodiesterase > GMP
-Protein > kinase > Protein-P > phosphatase > Protein
Termination: Ca2+ ions
Calcium ions reuptake back into ER or SER
Effect of cholera toxin on cAMP pathway
-causes inability to turn off cAMP pathway
-ingestion infects intestines
-cholera bacteria secrete cholera toxin and enters intestinal crypt cells
-toxin modifies G-protein > GTP cannot be hydrolyzed > irreversibly activates adenylyl cyclase > constant high levels of cAMP
-Cl-, Na+, K+, and HCO3- are secreted into lumen of intestinal cells and water follows salts leading to acute diarrhea, dehydration, and vomiting
-if untreated > death
