Chapter 15 Flashcards
2 methods of signal transduction
1) activation of receptors can transmit a signal ( g protein) to activate an enzyme (effector) that creates second messengers
2) activation of a receptor can cause it to change into a recruiting and docking station for other signalling proteins.
in most signaling pathways, proteins are activated by
phosphorylation/dephosphorylation
draw the mrna syntheiss signal transduction pathway
involves three PKs and a transcription factor
Activation of Receptor protein Tyr Kinases often results in ____ followed by activation of a protein kinase domain
dimerization
GPCRs interact with ____ proteins to activate an effect
G proteins
how is the inactive version of a GPCR stabilized? what happens when a ligand bind to the GPCR?
inactive conformation is stabilized by noncovalent interactions between AAs in the 7 helices. ligand disturbs the non covalent interactions, changing the conformation to Active State.
In what state does G protein bind to GPCR
GDP-Gprotein state
where does GDP/GTP bind to on the G protein
on G alpha subunit, causes dissociation and it binds to the effector to activate it, making the effector create second messengers
GPCRS bind specifically to ____ G proteins
heterotrimeric
when will G alpha subunit remove itself from the effector that it is activating?
when GTP hydrolysis occurs, amknig the Glpha back into GDP-Galpha. It will return back to the heterotrimeric form of G protein.
2 steps to GPCR de-sensitization
1) GRKs phosphorylate the G protein RECEPTOR, tagging it with a phosphate
2) arrestin proteins bind with the phosphorylated G protein receptor and compete with the actual G proteins for a spot on the GPCR.
Arrestin can also bind with AP2 adaptor proteins that are situated on RME clathrin coated pits, promoting the uptake of GPCR via endocytosis.
How does arrestin cause the GPCR to be absorbed into the cell?
In addition to acting as a competitive inhibitor at the binding site of the G protein on the GPCR,
Arrestin can also bind with AP2 adaptor proteins that are situated on RME clathrin coated pits, promoting the uptake of GPCR via endocytosis and end up in the endosome
How do Regulators of G protein signalling (RGSs) help with de-sensitization?
they help terminate the response of the effector by speeding up GTP hydrolysis of the G alpha subunit, deactivating the effector.
how does cholera target G proteins?
they inhibit the G alpha ATPase activity, and thus Atp is never hydrolyzed- the effector is always on and the intestinal tract will continue to secrete muscus, resulting in dehydrateion
2 main types of second messengers we studied
1) caMP
2) phosphatidyl inositol 2nd messengers
how are phoshatidyl inositol groups converted into second messengers
when ACh binds onto a GPCR resulting in G protein activation, the G alpha subunit activates a PHOSPHOLIPASE (PILC BETA), which can cleave a phosphatidyl insotiol phosphate molecule into DAG and IP3. DAG and IP3 are second messengers that trigger change in the cell
PI is phosphorylated by ___, creating PIP(4). PIP is phosphorylated by ____, creating PIP2(4,5). PIP2 is phosphorylated by ____,creating PIP3 (3,4,5).
PI is phosphorylated by PI4K, creating PIP(4). PIP is phosphorylated by PI5K, creating PIP2(4,5). PIP2 is phosphorylated by PI3K,creating PIP3 (3,4,5).
where are the phosphotidyl inositoll groups located when they are being phoshphorylated?
located in the membrane.
Which phosphatidyl inositol derivative is located broken down into DAG and IP3? Which PI derivative is responsible for the insulin response?
PIP2, PIP3.
PILC, and effector that gets activated by a G protein, cleaves PIP2 into ___ and ____
DAG and IP3
What does IP3 do?
binds to an IP3 receptor in the smooth ER which triggers to outflux of Ca2+ ions into the cytosol, which can trigger different events in a cell (muscle contraction, exo and endocytosis, etc)
What does DAG do?
remains in the plasma membrane and activates the PKC effect, to phosphorylate other target proteins
glucagon and epinephrine bind onto _____ receptors
Different types of GPCRs (ex/ beta adrenergic receptors)
the binding of glucagon or epinephrine onto a GPCR triggers the activation of a ____ (effector), which produces cAMP.
the G protein activates adenylyl cyclase, which produces cAMP from ATP.
glycogen synthase converts ____ into ____
glycogen phosphorylase converts ____ into ____
glycogen synthase converts UDP-Glucose into Glycogen
glycogen phosphorylase converts Glycogen into GLucose-1-Phosphate
glucagon is produced in the ____ cells of the ____, whereas insulin is produced in the ____ of the ____
glucagon is produced in the ALPHA cells of the PANCREAS, whereas insulin is produced in the BETA of the PANCREAS
anabolic enzymes are ____ when phosphorylated. Catabolic enzymes are ____ when phoshphorylated
anabolic enzymes are DEACTIVATED when phosphorylated. (EX/ GLYCOGEN SYNTHASE
Catabolic enzymes are ACTIVATED when phoshphorylated (PHOSPHORYLASE KINASE, GLYCOGEN PHOSPHORYLASE)
CAMP is broken down into AMP via
phosphodiesterase
Draw the pathway from glucose metabolism in response to glucagon
1) glucagon binds to GPCR, which recruits GDP-Gprotein. 2) GDP-G protein gets converted to GTP-G protein, and the alpha subunit dissociates and binds to adenylyl cyclase effect
3) adenylyl cyclase catalyzes ATP to cAMP
4) cAMP activates PKA
5) PKA can do three things:
- move to nucleus and phosphorylate CREB TF, which gets activated to create proteins involved with gluconeogenesis
- phosphorylate glycogen synthase, which de activates it and thus there is no more glycogen synthesis
- phosphorylate phosphorylase kinase, which will activae it. phosphorylase kinase will phosphorylate glycogen phosphorylase, activating it, thus triggering glycogen breakdown.
3 things that activated PKA can d0
- move to nucleus and phosphorylate CREB TF, which gets activated to create proteins involved with gluconeogenesis
- phosphorylate glycogen synthase, which de activates it and thus there is no more glycogen synthesis
- phosphorylate phosphorylase kinase, which will activae it. phosphorylase kinase will phosphorylate glycogen phosphorylase, activating it, thus triggering glycogen breakdown.
3 things that activated PKA can do
- move to nucleus and phosphorylate CREB TF, which gets activated to create proteins involved with gluconeogenesis
- phosphorylate glycogen synthase, which de activates it and thus there is no more glycogen synthesis
- phosphorylate phosphorylase kinase, which will activae it. phosphorylase kinase will phosphorylate glycogen phosphorylase, activating it, thus triggering glycogen breakdown.
what enzyme would be needed in order to increase glycogen synthesis
glycogen phosphatase would DE PHOSPHORYLATE glycogen synthase, activating it, thus allowing for glycogen synthesis.
in the liver, cAMP triggers ____
in the fat cells, cAMP triggers ____
in the smooth muscle cells, cAMP _____
in the liver, cAMP triggers GLYCOGEN BREAKDOWN and INCREASED GLUCONEOGENESIS
in the fat cells, cAMP triggers TAG BREAKDOWN
in the smooth muscle cells, cAMP Decreased relaxation
How are PKAs held down to specific regions of the cell?
using PKA anchoring proteins called AKAPs. AKAPs concentrate PKA to a certain region and concentrates its substrates to the same region so that
rhodopsin is an example of a
GPCR, and is responsible for black and white vision because it interacts with transducin g protein
when a GPCR is too active, it is considered a _____
gain of function mutation
when a GPCR is too insensitive to a ligand and cannot recruit G proteins when activated, it is considered a ____-
loss of function mutation
enzymes that phosphorylate tyrosine resides on target proteins
protein tyrosine kinases
example of a protein tyrosine kinase
receptor tyrosine kinases
ligand mediated dimerization versus receptor mediated dimerization
ligand mediated: a BIVALENT ligand attaches to 2 RTKs at the same time, causing the two receptors to dimerize. Dimerization exposes the kinase sites of the two receptors and they trans autophosphorylate each other.
receptor mediated: binding of one monovalent ligand to each of the 2 RTK’s triggers dimerization. Dimerization exposes their kinase site and they trans auto-phosphorylate each other.
the RTK dimers are now phosphorylated and active. they can act as recruiting stations for proteins to bind onto or they can phosphorylate other molecules
which type of domain is required in order for a protein to be able to bind onto a tyrosine kinase?
SH2 or PTB domain
RTKS contain ________ which allows a dimer to phosphorylate itself via trans autophosphorylation
intrinsic Tyr kinase activity
