Cell Signalling III Flashcards
PRO tyrosine kinase
phosphorylates target PROs at particular tyrosines
what is the diff b/w a RTK & GPCR?
GPCRs have 7 transmembrane segments
RTKs have a single transmembrane segment, but each RTK functions as a dimer so it has a total of 2
RTKs are involved in the regulation of what processes?
Growth (growth factor receptors), trigger mitosis
Cell division (defects lead to cancer)
Cell survival and death (programmed)
Cell attachments, migrations
what are the 2 ways RTKs dimerize?
1 ligand binding to both monomers (ligand causes dimerization)
each monomer binds their own ligand & the 2 monomers come together
what does dimerization trigger in RTKs?
auto-phosphorylation
the 2 monomers phosphorylate each other
when is insulin produced?
when blood glucose increases
where is glucose uptaken?
liver
muscle
fat cells
what effect does insulin have on BG?
decreases BG
what process is inhibited in the uptake of glucose?
gluconeogenesis
what cells make insulin?
beta
what cells make glucagon?
alpha
what does glucagon induce?
gluconeogenesis
what is unusual about the insulin receptor?
remains as a dimer before binding the ligand
structure of insulin receptor?
heterodimer
2 alpha chains - extracellular, ligand binding
2 beta chains - transmembrane, kinase activity (RTK)
alpha & beta are linked through disulfide bridges
what 2 processes occur when insulin binds to the receptor?
auto-phosphorylation
phosphorylation of the Insulin Receptor Substrate (IRS)
steps of insulin RTK
- Insulin (ligand) binds on the exterior of the cell to the alpha chains
- Tyrosine kinase activity Auto-phosphorylation & phosphorylation of Insulin Receptor Substrate (IRS)
- Other PROs bind & are activated by phosphorylated tyrosines on the RTK & IRS
- Stimulation of glycogen synthesis:
a. Cell proliferation (growth factor)
b. PRO kinase B induces movement of glucose transporters to move to the PM by vesicle movement
i. Glucose is taken up via facilitated diffusion
ii. Glucose is phosphorylated upon entry into the cell (maintain the gradient)
iii. Glycogen synthesis is stimulated
what events occur in diabetes? & how?
high levels of glucose in blood
loss of glucose in urine
excessive loss of water from frequent urination
high blood pressure
BG will remain in the blood & cause the pancreas to work harder to excrete it, so it does it by urination, glucose acts as a solute in the blood & pulls water out
type I diabetes
no insulin is produced by the pancreas
auto-immune disorder where beta cells producing insulin are destroyed
type II diabetes
insulin resistance in cells that should take in glucose
beta cells are still present, but the receptors fail
what is the diff b/w diabetes I & II?
I –> no beta cells, no insulin
II –> beta cells, insulin produced
what causes the loss of sensitivity in diabetes?
Faulty receptor
Faulty intracellular signaling (downstream events fail to occur properly)
what is a method of restoring insulin sensitivity?
removal of PRO tyrosine phosphatase (PTP) through gene knockout
what occurred in PTP gene knockout mice?
muscle cells remained with activated receptors where signaling is continually occurring –> glucose levels remained low
mice were fed rich diets without becoming obese
growth factor/cytokine
naturally occurring substance capable of stimulating cellular growth, proliferation and cellular differentiation
epidermal growth factor (EGF)
growth factor that plays an important role in the regulation of cell growth, proliferation, and differentiation by binding to its receptor EGF
what does an EGF activate/signal to occur?
changes in gene expression, prepare for mitosis
transcription factors are activated, genes involved in proliferation are transcribed
how is an EGF signal turned off?
EGFR is ubiquitinated
sent to lysosome for destruction or goes back to the PM
when is Ca2+ the 1st & 2nd messenger molecule? & what does this accomplish?
Ca2+ induced Ca2+ release
rapid amplification & coordination
Ca2+ induced Ca2+ release
Ca2+ released from internal vesicles in response to Ca2+ channels being placed on the cell surface
what are the types of Ca2+ responses?
voltage dependent channels in nerves & some muslces
receptor-mediated Ca2+ channels
how does calcium prevent polyspermy?
Sperm burrow in with lysosomal enzymes
Once the sperm hits the membrane, it triggers the influx of calcium event
Vesicles move the perimeter of the egg preventing entry of sperm done through Ca2+ induced Ca2+ release
Steps of Ca2+ induced Ca2+ release
Ca2+ enter through voltage gated channel on PM
Ca2+ binds to ryanodine receptor on SER
Ca2+ released from the SER through the ryanodine receptor (down conc gradient)
Ca2+ bind to calmodulin when out of the SER
Activated calmodulin binds to many other effectors
Effects include:
Movement of vesicles to the perimeter of the egg to prevent polyspermy
Pumping of Ca2+ out of the cytoplasm to the SER, the vacuole & exterior of the cell (active transport)
ryanodine receptor serves as what 2 functions?
receptor & channel
Nitric oxide (NO)
inorganic gas, can act as an extracellular messenger & 2nd messenger
what does NO induce the production of?
cGMP
activates guanylyl cyclase to make cGMP
where is NO synthesized?
NO synthase within cells
what type of hormone does NO act as?
paracrine & autocrine
NO’s role in the blood
acetylcholine can induce NO synthase
Production of cGMP causes smooth muscle cells to relax … slows blood flow by relaxing arteries
what is given to patients with heart probs & why?
nitroglycerine
produces NO to relax arteries
how does viagra have its effect on the body?
viagra is a drug that inhibits cGMP phosphodiesterase to relax blood vessels
how does the amplification of a signal work?
one receptor can activate several GPROs & each GPRO can activate several effector molecules
what are the 2 kinds of coordination?
spatial coordination
coordination of diff responses
spatial coordination
throughout the cell by diffusion of 2nd messengers (ex: cAMP, Ca2+ –> small molecules that diffuse fast)
coordination of diff responses
a number of diff enzymes have to work together to accomplish metabolic pathways
(ex: cell division –> needs a lot of things prepared)
what dies each signaling pathway provide?
an opportunity for cross talk b/w diff signaling pathways
what does the cell accomplish in cross-talk?
integrates information from many different signaling pathways to initiate an appropriate response
what is an ex of when cross-talk signals interfere?
when epinephrine induces gluceogenesis, PKA can inhibit the growth factor signaling pathway
epinephrine overrides growth factors, when there’s a stressful situation survival is more important than growth
convergence
2 receptors cause the same secondary signal to be activated –> 2 pathways converge to give one unified response
Ex: glucagon & epinephrine hit 2 diff receptors but induce the same response
divergence
one ligand has several effects or one signal propagates several responses
Ex: PKA turns on 3 diff PROs in gluceogenesis
crosstalk
pathways interconnect
2 pathways from diff hormones give confusing messages (work together or in opposition) Cell receives combos of signals that can trigger diff signaling pathways
what are exs of compartmentalization of a signal?
PKA is held in place by special binding PROs called AKAPs
scaffolding PROs
how a cell responds to a signal depends on: (3)
number of receptors
number of other signals
type of cell (b/c different cells have different downstream signaling molecules)
how does the cell compensate for having so many GPCRs but so little G PROs?
the same intracellular signaling pathway causes diff effects in diff cell types b/c the diff cells have diff downstream PROs to respond to the signal
