Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
27 Cards in this Set
- Front
- Back
7TM receptors consist of...
|
7TM receptor (always specific), heterotrimeric G protein (alpha unit with GDP/GTP, beta and gamma units)
|
|
upon binding of epinephrine to epinephrine receptor, what happens?
|
Galpha subunit trades GDP for GTP and dissociates from receptor, beta and gamma subunits dissociate, Galpha binds to adenylate cyclase, which turns ATP into cAMP
|
|
cyclic AMP
|
second messenger
activates protein kinase A opens up its catalytic sites that are normally blocked by pseudosubstrate |
|
what kind of amino acids does protein kinase A phosphorylate?
|
serine and threonine
|
|
epinephrine promotes...
|
-phosphorylation and activation of glycogen phosphorylase
-phosphorylation and inactivation of glycogen synthase -phosphorylation and activation of triacylglycerol lipase (induces lipolysis--breakdown of triacylglycerides) |
|
how are 7TM receptors inactivated?
|
1) Galpha subunits have intrinsic GTPase activity, so hydrolyze GTP to GDP and GDP-Galpha re-associates with rest of trimer
2) dissociation of ligand from receptor 3) kinases phosphorylate unoccupied carboxyl tail of receptor/hormone complex, this allows beta-arrestin to bind which blocks any more Galpha proteins from being activated |
|
7TMRs and phosphoinositide cascade
|
1) G-proteins activate phospholipase C
2) phospholipase C cleaves PIP2 into IP3 (soluble and diffiusible) and DAG (membrane associated) 3) IP3 releases Ca2+ from intracellular stores 4) DAG and Ca2+ activate protein kinase C |
|
2 reasons Ca2+ make a good second messenger
|
1) present at very low levels in cells, so can changes are easily detected
2) binds with high affinity to proteins to induce conformational changes |
|
calmodulin
|
activated by Ca2+
has 4 Ca2+ binding sites member of EF-hand protein family (helix-loop-helix) diffusible allosteric effector |
|
2 examples of calmodulin use
|
CaM-kinase: when calcium binds to calmodulin, they bind to CaM kinase to activate it
phosphorylase kinase: calmodulin is integrated into subunit, requires Ca2+ and phosphorylation to be completely active (this phosphorylates and activates glycogen phosphorylase) |
|
Cholera
|
toxin turns Galphas to a permanent ON state, so continuous activation of adenylate cyclase and PKA; intestinal PKA regulates activity of Cl- channels and Na/K exchanger; deregulation of ion transport resulting in massive loss of NaCl and water
|
|
Whooping Cough
|
Galphai normally inhibits adenylyl cyclase
this toxin traps G-protein in OFF state (can't exchange bound GDP for GTP) adenylate cyclase is now DIS-inhibited (made active) leading to increased levels of cAMP, altered regulation of Ca2+ and K+ channels |
|
the Insulin Receptor structure
|
receptor tyrosine kinase
dimer, each subunit consisting of alpha and beta subunit alpha and beta linked by a disulfid bond 2 alpha subunits form insulin binding site, beta subunit includes protein kinase domain |
|
what happens upon insulin binding?
|
-forces beta subunits together, which phosphorylate tyrosine residues in activation loops
-these phosphorylated sites serve as docking sites of insulin-receptor substrates (IRS) -docking of PI3K to IRS proteins localizes enzyme to membrane where it can phosphorylate PIP2 to PIP3 -PIP3 activates PDK1 which phosphorylates (activates) Akt (protein kinase B; not membrane bound) |
|
effects of insulin on glycogen synthesis
|
insulin activates PI3K/Akt signaling
protein kinases phosphorylate and INACTIVATE glycogen synthase kinase so glycogen synthase remains active |
|
inactivation of insulin receptor by phosphatases
|
protein tyrosine phosphatases dephosphorylate receptor
protein ser/thr phosphatases desphosphorylate Akt, etc. PTEN dephosphorylates PIP3 |
|
EGF receptor structure
|
exist as monomers--each unit binds one molecule of EGF
EGF binding causes dimerization kinase is always active, but can only interact with its substrate after dimerization |
|
Ras
|
small G-protein activated by EGF binding to receptor
when it trades GDP for GTP, becomes activated can bind to and activate protein kinases promiscuous--activates many different things |
|
EGF receptor signal termination
|
Ras has intrinsic GTPase activity
GTPase-activating proteins facilitate GTP hydrolysis |
|
Ras and cancer
|
Ras is frequently mutated in cancer
mutations can lead to an inability to hydrolyze GTP so leave Ras in permanent ON state |
|
Rous sarcoma virus
|
-normal signaling of receptor tyrosine kinase is terminated by tyr phosphorylation
-protein introduced by virus lacks tyrosine, so is always active -leads to unregulated growth |
|
if EGFR is overexpressed in cancer (usually epithelial cancers), what can be done to treat it?
|
Cetuximab competes with EGF for binding site on receptor and blocks ligand-receptor interactions (monoclonal antibody)
|
|
if Her2 receptor is overexpressed in breast cancer, what does overexpression promote and what can be done to treat it?
|
promotes signaling in absence of EGF
Trastuzumab inhibits Her 2 activity (monoclonal antibody) |
|
for steroid hormones, ligand binding does what?
|
induces a shift in conformation
conformational change at helix 12 creates binding site for coactivator coactivators facilitate changes in gene expression by modifying chromatin structure and recruiting RNA polymerase |
|
adenylate cyclase
|
changes ATP into cAMP upon activation by g proteins
|
|
protein kinase a
|
phosphorylates at ser and thr residues
activated by cAMP |
|
4 examples of second messengers
|
IP3, DAG, Ca ions, cAMP
|