Regulators of G-protein signaling and they can affect the rates of alpha subunits
What is GEF? What effect does it have on GTP? GDP?
Guanine Nucleotide exchange factors. Increases GTP and decreases GDP
What is GDI? What effect does it have on GTP? GDP?
Guanine nucleotide dissassocian inhibitor. Decreases GTP and increase GDP
What is GIP? What effect does it have on GTP? GDP?
GTPase inhibiting protein. Increases GTP and decreases GDP
What is GAP? What effect does it have on GTP? GDP?
GTPase activating protein. Decreases GTP and increases GDP
What is Protein Kinase A dependent on? what are some of its functions?
it is a cAMP dependent...regulation of glycogen, sugar, and lipid metabolism
What is signal transduction?
Passage of a signal going from one form to another
Explain notch and delta
signals are not actually released but require physical contact as with membrane bound signals.
Describe endocrine messaging
when chemical messengers are released into circulation
describe paracrine and autocrine
paracrine is when chemical messengers are released and affect neighboring cells autocrine is when messengers are secreted and it affects the cell that secreted it
describe messaging in neurons
chemical messengers can be released by neurons across synapses to affect other neurons or effectors such as muscles or glands
what is an amplification stage?
when one activated primary effector produces many molecules of secondary messengers which can effect many target proteins.
Are the chemical pathways fairly linear?
No, there is extensive convergence and divergence of pathways producing significant cross talk between pathways which is necessary to integrate cell function.
Is it likely that a cell in the body is only subject to one messenger at a time?
NO, typically cells are exposed to a constantly changing cocktail of chemical mediators whose effects may change as the target cell itself does
How many general signal transduction mechanisms are there and name them
There are 4. Ionotropic, Metabotropic receptors and heterotrimeric g-proteins, metabotropic receptors and low molecular weight g-proteins (RTK's), and intracellular receptors
If a chemical messenger does not get into the blood stream then it is not:
How do excitable cells such as neurons and muscle cells operate?
What is a way that Ca can enter a cell directly? Explain the process\
Calcium ions can enter a cell through an ionotropic receptor and bind to and activate specific calcium binding proteins intracellularly (such as calmodulin).
When does calcium act as a secondary messenger? What kind of effect does the calcium have on membrane potential?
it acts as secondary when it enters the cell via the ionotropic receptor. the result is negligible
What is the best example of ionotropic receptor mechanism? Where is it found?
Nicotine Acetylcholine receptor found at neuromuscular junctions (skeletal muscle), autonomic ganglia and the brain
What mechanism does adrenaline (epinephrine) and most peptide hormones work off of?
Metabotropic Receptors and Heterotrimeric G-proteins
What do GPR's determine? What do odorant GPR's allow us to do? Where were they identified from?
they determine specificity. the odorant ones allow us to dicriminate between many different odors. They were identified from the human genome
Acetyl CoA forms how many ATP's? NADHs? FADH2's?
1 ATP, 3 NADH's, 1 FADH
What type of tails do the alpha and beta/gamma subunits have and why?
lipid tails, which ensures that they are correctly located on the inner face of the cell membrane.
What can increase the rate of hydrolysis of the g-proteins?
Regulators of G-protein signaling
Where are G-proteins found?
Some are expressed ubiquitously in all cells and are involved in fundamental/universal cellular functions while others are only found in specialized cells where they are only apart of a specialized function
There are hundreds of GPRs involved in odor dicriminaton but how many G-proteins? What is/are the name(s)? How is the specificity given?
one; G-olf; by the GPR and the specific "wiring" of the neurons
What do secondary messengers affect? What is the best example of this and why?
the activity of target proteins; best example is protein kinase A which is activated when cAMP binds to inhibitory subunits which then allows it to affect many targets via phosphorylation (amplification)
What causes deactivation of cAMP and cGMP?
what determines the actual amount of secondary messengers?
the relative activity of both the activating and degrading enzymes producing graded responses
RTK's are not functional until...
the binding of the messenger extracellularly brings 2 receptors close together (dimerization)
Why are RTKs important?
They often regulate growth and differentiation, if you do not regulate growth correctly you can get cancer
What does tyrosine kinase do in RTKs? What reverses this?
phosphorylate specific tyrosine residues and this is reversed by phosphotases
What does RAS control?
What does Rac control?
What does Rab control?
vessicle transport and exocytosis
What does Rho control?
What does Ran control?
RTKs once phosphorylated can specifically bind proteins that apparently have no intrinsic activity however...
these are still extremely important as they form the molecular scaffolding binding other proteins that otherwise would not and helping form functionnal macromolecular complexes. They help ensure pathway components are in the right place as with the GEF needed to activate Ras.
What chemical messengers can cross the cell membrane? What happens to these messengers once inside the membrane?
all the steroid hormones and thyroid hormones, NO and CO have also been identified as messenger molecules; once inside they are recognized by intracellular receptors either in the cytoplasm or nucleus itself
Upon binding to their specific receptors what occurs next with intracellular chemical signals?
both the chemical and specific receptor move into the nucleus (unless it is already there) and acts as transcription regulators
What produces NO?
the enzyme Nitric Oxide Synthase (NOS)
Can NO and CO be stored?
No, they are generated on demand similarly to all of the steroid hormones
How many TMDs does an activated RTK have?
How do GPRs activate heterotrimeric G-proteins?
causing an exchange or bound GDP for GTP
How do heterotrimeric G-proteins activate their primary targets?
How do heterotrimeric G-proteins "cycle"/inactivate?
by conversion of bound GTP to GDP due to intrinsic GTPase activity of alpha subunit
Can this be affected/altered?
the rate of hydrolysis can be altered by RGSs
So the alpha subunit limits the life of both active parts of the heterotrimeric G-protein?
What activity does an activated RTK have?
phosphorylatinf specific tyrosine residues on its partnerin RTK (auto cross phosphorylation)
Can Ras self regulate?
How does it regulate?
Via accessory proteins (GEF, GDI, GIP, and GAP)
Do all RTK initiated pathways involve RAS?
No, some kinase cascades are activated directly by RTKs
How are overall cAMP levels determined? (think simpler!).
The balance between cyclase and phosphodiesterase activity.
How is the activity of proteins affected by phosphorylation regulated overall? (think simpler!).
The balance between kinases and phosphatases.
What potential targets might a kinase (like PKA) have? (think simpler!).
Many such as enzymes, ion channels, transporters, transcription, translation.
Phospholipases typically produce what kind of 2o messenger?
Lipids and lipid derivatives like DAG and IP3.
What is the most well known �receptor� for nitric oxide?
NOS is generally activated by __1__. NOS synthases uses __2__ to __3__ __4__. NOS's target is soluble __5__ which then stimulates production of __6__.