Cell Signaling Flashcards
What are the steps of cell signaling
Hydrophillic signals attach to then make it active cell surface receptor
The signal then moves to transduction protiens and second messengers
This signal then goes to an effector protien
What can an effector protien do
Modify cellular metabolism, function, movement or go into the nucleus that then effects gene expression, development
What are the four forms of intercellular signaling
Endocrine signalling (blood vessel)
Autocrine
Paracrine signalling
Signalling by plasma membrane-attached proteins
What is autocrine signaling
Targets sites on same cell
What is paracrine signaling
When one cell secrets a chemical affecting neighboring cells
What is endocrine signaling
Process by which hormones are reeleased from the endocrine glands and diffuse through the blood
Can signaling molecules act in both endocrine and paracrine signaling
YES in epinephrine
What is a nuclear superfamily
What is in the cytoplasm and what is in the nucleus
Inter cellular and can cause an effect in the nucleus usally is composed of a family of transcrption factors they have highly conserved DNA binding regions and ligand binding regions
Cytoplasm- Estrogen, Progesterone and Glucocrticoid
Nucleus- Thyroxine and retinoic acid
How does the glucocorticoid receptor work
It is on the DBD and there is an inhibitor which is HSP90 on the LBD when the hormone comes it it removes the inhibitor and now it can bind to certain promoter sequences
How does the receptor get into the nucleus from the cytosol
It is hydrophobic so it can cross the membrane
What is the basic pathway of transduction
- You have an extracellular signal molecule that binds to the ligand
- Then you have a cytoplasmic portion
- It then goes to the intracelllular signaling protiens or molecules
- This will then effect effector protiens
What is considered the primary messengar in signal transduction
THe extracellular signal molecule
What are some examples of effector protiens and what do they effect
There 3
Metabolic enzyme- alterd metabolism
Gene regulatory- altered gene expression
Cytoskeletal protien- altered cell shape or movement
What are the steps in signaling by cell surface receptors
- Synthesis and release the signaling molecule by the singlaing cell
- transport and binding the signal to a specefic receptor of the target cell which result5.s in change of confirmation
- Initation one or more intracellular signal-transduction pathways
- Short term cellular response
- Long-term cellular responses
- Termination of cellular response
What are some examples of fast cellular pathway
Changes in ion transport, cell movement, secretion or metabolism
What are some slower pathways
Gene regulated changes in cell growth and divison
What are the 4 extracellular signal molecules
- Survival signals
- Growth and divide
- Differentiatie
- Die
What are the two signals of aptosis
- Removal of survival factors
- Death signals
What is binding speceficity based on
Molecular complementarity between the interacting surfaces of receptor and and ligand (non covalent forces)
Along with having corresponding charges
What can signaling molecules also do
Signaling molecules or ligans can induce receptor dimerixation where an additional receptor comes in
What is the disocation constant
Kd= (R)(L)/(RL)
How do you get R and L
adding them together
What is kd the measure of
Affintiy of a receptor to its ligand it is the ligand concetration that is required to bind 50% of the cell surface receptrors
What does a smaller Kd mean
The lower the ligand concentration required to occupy 50% of the cell surfac receptors
How can you tell what sequence is expressing for a certain receptor for a ligand
You take a cell that has that has that receptor and then you
Insert the cell with cDNA library and screen for cellular phenotype associated with that ligand
Identify the incorporated cDNA by PCR followed by sequencing
The receptor protein can be deduced from the cDNA sequence
Can then mutate specific amino acids to determine essential ligand binding domain
What are the three type of kinases
- Tyrosine Kinases
- Serine/Threonine Kinases
- Dual Kinases which cna do all three
What are the three types of phosphatases
- Tyrosine Phosphatases
- Serine/Theronine Phosphatases
- Dual Phosphatases
What do kinases and phosphatases do
Kinase puts on phosphates
Phosphatases removes phosphate groups
What can you tell from phospho-specefic antiobodies
They can reveal activation of signal transduction pathways the more you have phosphates from (kinase) it will create an increase in production of the protien
What are the forms that G protien exist in
- Active-bound to GTP
- Inactive-bound to GDP
How do you go from inactive to active form
You have to be able to remove the GDP form you can do this by using GEF which is an activator protien that replaces GDP with GTP
How do you go from the active form to an inactive form
You have to hydrolyze the GTP and you can do this with the help of GAP which is a GTPase
Are the gates opened in the active state
No they are opened in the off state
How many domains are in a protein coupled receptors
7
What are the three subunits of the G-protien complex
Ga Gb and Gg
What protiens are lipid anchor in the G complex
Ga and Gg
What are the steps ot activate GPCR
You have agonist binding to an inactive receptor
The G protien in inactive because it is bound to GDP
When the receptor is active it will bind to the alpha unit
Dissociaton of GTP to GDP occurs
The alpha unit then dissocates from the B and Y sub unit
The GTP complex with the alpha unit attach to an effector protien
Hydrolsis of GTP alllows the alpha to go and rejoin the Gb and Gg and it restarts
What happens when to the B and Y sub unit when the alpha dissocates
Can sometimes bind to an ion channel and it usually is going to open an ion channel but this can be a rare event
What is CAMP
acts as an extracellular signalling molecule that can binds to and signals via a G protein coupled receptor
How cna you demonstrate how a receptor mediated dissociation of Ga and GBG using FRET
The Ga of the comples is bound to the CFP protien and GB fuses with YFP
When they are close together in other words are not dissociated they release the yellow light
But when it switches to GTP form where the ligand binding leads to dissociation no more ressoance energy
What would the line graph look like between cAMP being added and the ammount of yellow light
At first there would be a high amount of yellow light an then has time progressed and more ligand became bound it decrease in the ammount of light
