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20 Cards in this Set
- Front
- Back
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What are the 3 classes of single-pass receptors?
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TGF-beta
Cytokine RTK (receptor tyrosine kinases) |
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Cytokine receptors - what's the first step that must happen to the intracellular domain to propegate the signal?
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Receptor dimerization - the intracellular domains end up coming together
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What protein kinase should i immediately think of when talking about cytokine receptors? Is it INTRINSIC or EXTRINSIC? What is its function?
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JAK (janus tyrosine kinase) - dimerization phosphorylates it.
IT IS EXTRINSIC - not part of the receptor. This goes on to phosphorylate additional residues ON THE INTRACELLULAR RECEPTOR |
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How is the signal from a cytokine receptor, through JAK, turn into increased gene transcription?
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JAK/STAT pathway - STAT (signal transducer and activator of transcription) is a TF. Phosphorylation by JAK causes it to dimerize and translocate into the nucleus - turn on genes!
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Give 3 examples of types of cytokine signaling and what they induce
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1. Interferon response - viral infection causes interferon secretion, stims antiviral response
2. Prolactin - pregnancy = prolactin secretion, prepares mammary glands for milk-makin' 3. Erythropoetin - causes hematopoetic cell differetiation into red blood cells |
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What are the two pathways you can use to stop the erythropoetin signal?
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Think SHP1/SH2 and SOCs
SHP1/SH2 = short term, binds, dephosphorylates JAK. SOCs = long term, binds Erythropotein receptor, stops phosphorylation, also ubiquinates JAK for degradation. |
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How are RTK receptors like the cytokine variety?
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Ligand binding causes dimerization, ups kinase activity and results in phosphorylation. Receptor intracelluar domain ends up phosphorylated, serves as a docking station for other proteins that regulate gene expression
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How are RTK receptors unlike the cytokine variety?
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RTK receptors use an INTRINSIC tyrosine kinase, built into the receptor. No JAK.
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How is the RTK pathway associated with breast cancer? What drugs can be used?
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Think Her2. Human EGF Receptor (HER) gets mutated or is overactive and can heterodimerize when it's not supposed to = constant activation, seen in 25% of breast cancers. Even with low EGF, still get activation
Her2 Monoclonal Antibodies are a possible treatment. |
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What is the most commonly activated pathway associated with RTK receptors?
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Think Ras/MAPK
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RTK - Ras - MapK. What is Ras, and how does RTK interact with Ras?
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Ras is a MONOMERIC G-protein. Like other G-proteins, it needs to go from GDP to GTP bound form to be active. Needs intermediates - activated RTK binds GRB2 by its SH2 domain.
GRB2's other domain, SH3, binds SOS which binds RAS (acts like GEF), exchanges GDP for GTP and activates RAS. This goes on to use the MAPK. |
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How does Ras interact with MAPK? Again, all part of the RTK pathway.
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MAPK (mitogen activated protein kinase) is really made up of 3 steps - the final end is ERK. Ras activates RAF, which activates MEK, which activates ERK. Erk can enter nucleus, act as TF, turn on lots of stuff.
Ras-raf-mek-erk. |
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How is the Ras/MAPK pathway involved in cancer?
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This is the most often messed up pathway in cancer. Can see Ras mutants that can't hydrolyze GTP, so they're always turned on.
Mutation is in GLY-12 to anything other than proline |
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Once MAPK (erk, specifically) is in the nucleus, what protein does it interact with to turn on genes?
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Thing TCF/SRF/Fos
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What are some examples of RTK signaling? As in, what types of signals go through this pathway?
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Insulin receptor, Epidermal Growth Factor Receptor (EGFR), and Vascular Endothelial Growth Factor Receptor (VEGFR).
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TGFBeta receptors - How is a signal initially detected, and what are the first steps of signal transduction?
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TGFB binds its already phosphorylated receptor (RII), recruits RI coreceptor living next door and phosphorylates its ser/thr residues - this begins the cascade.
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TGFB/SMAD signaling - after activating the co-receptor (RI), what happens?
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RI coreceptor phosphorylates Smad3, complexes w/ Smad4 to enter nucleus and transcribe genes.
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What does the TGFb/SMAD pathway have to do with cancer?
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TGFB/Smad can transcribe CDKi's and other cell-cycle repressors - mutating the system may prevent this and allow unchecked cell division.
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TGFb signaling - aside from cancer, what does activating it lead to the secretion of?
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Extracellular matrix proteins = more stable tissues.
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What kind of disease is multiple sclerosis? What are some treatments?
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Autoimmune - need to decrease inflammation, use anti-inflamation steroids and interferon therapy.
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