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28 Cards in this Set
- Front
- Back
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what are the two categories of hormone receptors? give examples of one that picks up protein hormones. briefly describe how they work.
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1. membrane receptors. Detect peptide hormones (like GH, insulin, PTH) and catecholamines derived from tyrosine (norepi, epi, and dopamine).
binding of hormone causes intracellular domain to change confirmation, activating a second messenger. Can cause increases in cAMP/cGMP increase Ca++ channel opening, make membrane lipids become IP3 or DG (diacylglycerol), phosphorylate. |
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are protein receptors fast or slow to respond?
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they're fast - dont' depend on new proteins to be synthesized, but can later on make more synthesis.
don't initially cause anything to bind/unbind DNA. Can later (through CREB = cAMP-response element binding protein, binds CRE's in promoters) |
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talk about the other kind of receptor. what activates it, effects, etc
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sterpoid hormone receptors (glucocorticoids like cortisol, mineralcorticoids like aldosterone/androgen/estrogen).
lipid-soluble steroids pass through outer membrane and bind their receptor in the cytoplasm, which exists normally bound to HEAT SHOCK PROTEINS (hsp). HSP keeps the receptor in the cytoplasm. binding hormone makes receptor ditch HSP and the hormone translocate into the nucleus and bind HRE (hormone response element) in the promoter of gene of interest. Act to increase transcription - this is the primary reaction and can take hours/days for effect to take place. |
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what steroid hormone receptors show exception to this general outline?
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thyroid hormone receptor, estrogen receptor, and vitamin D receptor look like they don't normally sit bound to HSP's, but instead sit in the nucleus already attached to their HRE, keeping it inactive.
binding of steroid to the HRE stops repression. |
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what are potential second messengers?
what kinds of things can get phosphorylated? |
cAMP, cGMP, Ca++, IP3, DG.
amino acids can get phosphorylated (serine/threonine, and of course, tyrosine) |
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what two classes of enzymes add and remove phosphates?
what kinase does cAMP turn on? what does it work on? |
kinases add, phosphotases remove.
cAMP makes pKA go to work. pKA is a serine/threonine kinase. |
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what does cGMP turn on? what is its general effect?
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it turns on pKG, also a serine/threonine kinase.
cGMP/pKG generally cause vasodilation and VOLUME DEPLETION. |
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what makes pKC get turned on? what are its general effects?
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pKC is turned on by Ca++, maybe via diacylglycerol (DG).
pKC promotes cell division and is something that's often activated in cancers. think C = cancer |
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what's a calmodulin kinase? where is it found?
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Ca++ and calmodulin bind, and together they bind Calmodulin-Dependent Protein Kinase.
see this in the nervous system - the calmodulin-dependent protein kinase plays a big role in the upped Ca++ leading to release of neurotransmitters at nerve terminals. |
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there are lots of serine/threonine kinases. what's a tyrosine one? what signal should we think of? how do they look different? what do they initiate?
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insulin! it's binds a Receptor-Tyrosine-Kinase (RTK).
RTK's tend to have 1 membrane spanning domain and act through dimerization of receptors. These tend to increase intracellular Ca++, up the Na/H exchanger, and turn on PLCalpha (phospholipase C alpha). |
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how does a G protein coupled receptor work, generally?
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has an on and off switch - when it's on, it has a higher affinity for GTP which turns it into the active state. Active has a hydrolayze that eventually makes GDP and turns it off.
off state has a higher affinity for GDP, where it's not active. when active, can go to work on our second messengers (cAMP, CGMP, Ca++, Ip3, DG) |
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so when you get a hormone binding a receptor, what happens?
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G-protein coupled receptor gets activated, turns on an "effector" (which is likely to be adenylate cyclase, cGMP phosphodiesterase, Ca++ channel, or phospholipase C).
These turn on the secondary messegners (cAMP, cGMP, IP3, DG, Ca++) which work on second-messenger dependent kinases (PKA, PKG, PKC) |
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what physical classes of G-proteins are there?
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heterotrimeric (with the alpha, beta, and gamma subunits). THe beta and gamma subunits are attached tightly to each other and usually the receptor itself. The alpha subunit binds GTP and can move to the effector (adenylate cyclase) to cause signal transduction.
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what's different between Gs and Gi proteins?
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Gs are stimulatory. Get GTP binding and alpha subunit disassociation for activation of effectors.
things like adenosine can activate Gi proteins. Get same action: disassociation of alpha subunit. This time, though, the alpha causes ADNEYLATE CYCLASE to shut down. |
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how does cholera toxin work?
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forces ADP ribose transferring to Gs alpha subunit, keeping it active.
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what's Gq do?
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Gq can result in the formation of IP3 and DG.
IP3 causes opening of Ca++ channels. Ca++ and DG together cause activation of PKC. |
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what does phospholipase A2 do?
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works through G proteins to cleave membrane phospholipids into ARACHADONIC ACID, to make pro-inflamatory things.
note that it's ACTIVATED in a g-protein dependent method. |
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what's a monomeric G protein? what happens when activated/
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think RAS, RHO, and RAB. Ras works to increase transcription.d
Ras is turned on by GNRP (guanine nucleotide releasing protein), which helps get a GTP attached to it to make it active. Inactivated by GAP (GTPase activating protein). NOTE - common cancer pathway is when GAP doesn't work, can't hydrolyze the GTP and get permanent growth factor activation. |
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how is the growth hormone signal transmitted to the nucleus?
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Growth Hormone receptor has no intrinsic kinase activity, but binding GH causes it to dimerize and bind JAK.
JAK autophosphorylates when attached to activated GH receptor. This then acts on STAT to phosphorylate it, it disassociates and enters the nucleus to turn on genes. |
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Phosphotases: what is the major division? minor division?
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like kinases, they're divided into
serine/threonine and tyrosine phosphotases. for the serine threonine, called PP1 and PP2. NOTE = PP2B is regulated by calcium/calmodulin and is also called CALCINURIN Tyrosine phosphorylases are sometime cytosolic and somtimes membrane bound (can be considered receptors) |
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how does ANP work?
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released from the atria, binds receptors to increase the excretion of salt and water. Also relaxes vascular SM.
Receptor is a single-domain, ups levels of cGMP, activates PKG. |
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how does NO work?
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released by endothelial cells and considered PARACRINE.
Dilates smooth muscles on the vessels. Activates cGMP too. Made by NO synthase enzyme, which turns ARGNINE into citrulline and NO. NO synthase depends on Ca++/Calmodulin to work! |
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what are some monomeric G proteins? what activates them?
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ras, rho rab.
they don't have 3 subunits. the growth factor receptor tyrosine kinases (IGF-1, etc) work through these to increase transcription factors NOTE - ras is mutated in nearly all cancers. |
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objective 9 - compare the phosphotases.
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two kinds : serine/threonine and tyrosine.
serine/threonine are broken into PP1 and PP2. PP2b is also known as calcanurin (it's regulated by Ca++ and calmodulin). tyrosine phosphatases - in both the cytoplasm AND plasma membrane. Has the ability to act as a receptor and be acted on by circulating things. |
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REVIEW:
monomeric g-proteins - what's weird about how they're activated/deactivated? |
they require helpers to get GTP attached to activate and GDP attached (hydrolysis) to inactivate.
GAP inactivates, GNRP activates. note that this pathway is how a lot of growth factors are transcribed. |
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review notes:
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monomeric g proteins are coupled to RTK's.
receptors are: seven pass, RTK's, GH, insulin alpha/beta RTK. PKC - generated by Gq's which make PLC which cleave PIP2 into IP3 and DAG, which let in Ca++ and make PKC active. Big in cell division, cancer. Ca++/Calmodulin kinases Insulin and IGF work through RTK's. RTK's can work through Ras and RHO. Insulin works through RTK and an IRS, PKB (PKB) and PKC. we have two RTK's for this class - insluin (turn on IRS) and IGF's. intracellular tyrosine kinase includes JAK and then STAT, activated by GH. adenosine and somatostatin work through Gi? phosphotases: the tyrosine can be a receptor (just like the kinase). the serine/threonine have the PP1 and PP2b kinds. phosphodiesterases shut down cGMP/cAMP, so viagra is a cGMP phosphodiesterase inhibitor. ANP is weird because it turns on guanyl cyclase through a SINGLE PASS ANP receptor that activates guanylate cyclase. NO synthesis from argenint to cirtulline and NO requires Ca/Calmodulin. |
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REVIEW:
monomeric g-proteins - what's weird about how they're activated/deactivated? |
they require helpers to get GTP attached to activate and GDP attached (hydrolysis) to inactivate.
GAP inactivates, GNRP activates. note that this pathway is how a lot of growth factors are transcribed. |
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review notes:
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monomeric g proteins are coupled to RTK's.
receptors are: seven pass, RTK's, GH, insulin alpha/beta RTK. PKC - generated by Gq's which make PLC which cleave PIP2 into IP3 and DAG, which let in Ca++ and make PKC active. Big in cell division, cancer. Ca++/Calmodulin kinases Insulin and IGF work through RTK's. RTK's can work through Ras and RHO. Insulin works through RTK and an IRS, PKB (PKB) and PKC. we have two RTK's for this class - insluin (turn on IRS) and IGF's. intracellular tyrosine kinase includes JAK and then STAT, activated by GH. adenosine and somatostatin work through Gi? phosphotases: the tyrosine can be a receptor (just like the kinase). the serine/threonine have the PP1 and PP2b kinds. phosphodiesterases shut down cGMP/cAMP, so viagra is a cGMP phosphodiesterase inhibitor. ANP is weird because it turns on guanyl cyclase through a SINGLE PASS ANP receptor that activates guanylate cyclase. NO synthesis from argenint to cirtulline and NO requires Ca/Calmodulin. |
