week 6 Flashcards
Why can lipidated proteins be considered “peripheral” membrane proteins?
A lipase can release the protein to the cytoplasm or extracellular space
what are examples of a Signal (Ligand)
Chemical, Light, Gravity, Sound, Electric field, Temperature
Chemical =
Molecular signals =
ligand
what does a receptor do?
senses a signal
what occurs when a receptor senses a signal?
A physical change occurs (typically protein conformation)
what is Transduction?
Signal is relayed through the cell usually via secondary messengers
what is an Effector?
target of signaling ( may be several in signaling pathway)
what is the Target?
Cellular response, Result of transduction
-May be a physiological change or change in gene expression
Cellular signals are usually_____
molecular
Signals can be from ___ or ____
environmental or cellular sources
Proteins, hormones, growth factors
Molecular signals are all
cellular signals
Environmental signals can be ____ or ____
molecular or physical
The females of many insects (like Gypsy moths) release a pheromone molecule that males can sense at very low concentrations. One method of controlling such insects is to spray a pheromone disrupter that mimics the pheromone. Such a disrupter, would be considered a_____________.
ligand
GPCR and Tyrosine Kinase are
Receptors
Binding of ligand to receptor is
specific and based on shape
Conformational change results in __
transmission of extracellular signal to intracellular signal
Which regions appears to be most altered upon binding ATP?
Blue
*What major structures are typically involved in conformational changes?
Disruption of R-group bonds result in different structural motif interactions
What are the G-protien subunits?
G alpha, G beta, G y
This releases G beta and G y
activated G alpha
G beta and G y
Act as signaling molecules
GPCRs are
Integral membrane proteins
what is the structure of a GPCR?
Extracellular ligand-binding domain
Intracellular G-protein coupled domain
when is GDP is bound to the G alpha
The G protein is off
when is GTP is bound to the G alpha
The G protein in on
what triggers binding of GTP to G alpha?
Conformation change of GPCR
The G-proteins we have discussed are also known as “large G-proteins” or “heteromeric G-proteins”. They associate with membranes through_____________.
interactions with GPCR
lipidation
The peptide sequence motifs in Worksheet 8 are an example of ______________ protein structure.
primary
Receptor Tyrosine Kinase (RTK)
Integral membrane protein that are monomer in the inactive state (unbound)
What happens when a ligand binds to a RTK
- Monomers dimerize
- Tyrosine kinase domain of protein is activated and phosphorylates tyrosines
- Other signaling proteins can be activated
What does Dimerize mean?
monomer + monomer = Dimer
Act as message relays
Second messengers
cAMP and IP3 are two common examples
Second messengers
cAMP
Usually associated with GPCR pathways
adenylyl cylcase
An enzyme stimulated by G alpha after ligand binding (to make cAMP)
what is used to make cAMP
ATP
What does cAMP target after activation
cAMP targets proteins - protein kinase A (PKA)
Phosphoinostiol System
- PLC (activated through G protein) cleaves the carbon chains of a phospholipid (PIP2)
- Results in IP3 ( lets Ca enter cytoplasm) and DAG (stays with membrane)
What function do (protein) kinases complete?
Add a phosphate to proteins
Kinases can be activated through
phosphorylation
Phosphatases
removing phosphate
signal amplification
A result from Kinase cascade activity
Many pathways use kinases to transmit information.
If a phosphatase that opposing the action of a critical kinase were to be inhibited then ___________.
the signal transmission would be enhanced
Avastin is a drug that is used in chemotherapy to stop the growth of cancer cells. It acts by inhibiting certain kinases. A cancer cell might acquire resistance to this drug by ____________.
decreasing the activity of phosphatases
Target proteins
carry out the response to a signal
target proteins can…
Can alter gene expression
Can alter existing proteins to cause a change
Can directly regulate cell growth by altering cell cycle or metabolism
If a ligand was present and enzyme at the A arrow was blocked, what would you predict? (ws9)
Kinase activity would remain the same and
PLA2 activity would remain the same
cPLA2 is directly activated by several insect venoms. If the enzyme at the B arrow were blocked during a bee sting, what would you predict? ( ws9)
Prostaglandin levels would rise and
COX activity would increase
If GTP was blocked from associating
with the molecule indicated by arrow A,
then __________________. 9
kinase activity would remain the same
If cellular PIP2 levels were decreased, then _________________.9
cytosolic calcium levels would remain the same?
Inhibiting the step noted by
the arrow “A” would
_____________.10
cause TAZ to build up in the cytoplasm
Inhibiting the step indicated by
arrow B, would__________.
cause cell density to increase
Hippo was first described by Drosophila geneticists. In the Drosophila field, new mutants are named after their phenotype. Why do you think these flies look like Hippos? 10
They are bloated with too many cells.
Activation of the membrane-associated ER caused cell growth and proliferation in ____tissue
Breast
Although this figure shows estrogen as the ligand, researchers used EDC. Why?
EDC only binds the membrane-bound receptors
What is the role of eNOS?
To produce nitric oxide
Activation membrane-bound ER caused vascular protective responses.
True