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| oncogenes have normal cellular homologues called |
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| retrovirus that confers a growth advantage on cells = cell transformation |
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| loss of contact inhibition (cells grow on top of each other instead of in a monolayer), indefinite proliferation (immortality), cells lose a need for serum growth factors, anchorage dependence is lost, glucose transport and glycolysis increase |
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| gene product that confers growth advantage on cells via rous sarcoma virus. = v-Src, a protein kinase specific for tyrosine (mutated c-src). homologue = c-Src = proto-oncogene. |
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Term
| protein kinases (like Src) first phosphorylate, (and then, and then) |
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Definition
| themselves, (then their dimer partners, then their substrates?) |
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| primary autophosphorylation site in c-src ____ kinase activity |
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| inhibits, vs. v-src which autoactivates |
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| a growth advantage on a cell infiltrated by a virus is also a growth advantage for |
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| t/f proto-oncogenes can undergo mutation without any viral transmission |
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| has pleiotropic effects on many cells; effects are mediated by EGF receptor, which is a tyrosine kinase |
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| growth stimulation, metabolic regulation, augmented nutrient transport, differentiation, post-natal eye opening and tooth development in mice |
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| prototypical receptor tyrosine kinase structure (4) |
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Definition
| (RTK) Extra-cellular binding domain, transmembrane region, tyrosine kinase domain with ATP and substrate binding regions, intracellular domain contains tyrosine autophosphorylation sites and serine/threonine phosphorylation sites |
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Term
| steps in EGF signaling (typical for all tyrosine kinases) (3) |
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Definition
| dimerization followed by trans-phosphorylation of the tyrosine kinase domains, which activates the receptor's ability to phosphorylate its subsstrates on tyrosine. |
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Term
| autophosphorylation of the C-terminus |
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Definition
| allows that part of the protein to move away from the ATP-binding domain, thus activating the (kinase) protein |
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Term
| threonine phosphorylation |
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Definition
| shuts off tyrosine kinase; negative feedback loop |
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| oncogene that is a truncated (nonregulated) form of EGFr; does not require EGF for activity. = unregulated tyrosine kinase = always on, causes many cancers, like breast cancer |
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| avian erythroblastosis virus |
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Definition
| requires erb b to cause cancer |
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Term
| RTKs / how are they grouped |
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Definition
| receptor tyrosine kinases: ligand-regulated PY activity modulated by ser/thr phosphorylation. receptors bind with signaling molecules, interacting directly with them. grouped based on structure: number of subunits, presence of cysteine-rich domains (primary structure similarities), number of py domains, etc. |
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Term
| RTK signaling mechanisms (4) |
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Definition
| direct activation of signaling enzyme by tyrosine phosphorylation: phospholipase c-gamma. conformational change of an enzyme's regulatory subunit leading to localization and activation of the catalytic subunit: PI3K. formation of multisubunit signaling particles that activate small g-proteins. direct activation of transcription factors: jak/stat |
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Definition
| catalyzes the hydrolysis of PIP2 to IP3 and diacylglycerol, which then move down different pathways. |
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Definition
| enzyme catalyzes the addition of a phosphate group to a number of PIs (enzyme itself is not phosphorylated; docking is what causes conformational change), which when phosphorylated on the 3rd position can activate downstream signaling kinases. p85 and p110 work together. |
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Term
| formation of multisubunit signaling particles that activate small g-proteins: activating Ras. |
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Definition
| RTK is activated and phosphorylates Shc, which binds to Grb2. this complex binds to SOS. the activated SOS induces exchange of GTP for GDP. the activated Ras recruits a ser/thr kinase to the cell membrane, which activates an intermediate kinase which activates MAPK >>> cell cycle |
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| protein-protein interactions in response to tyrosine phosphorylation depend on several |
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Definition
| well-characterized structural motifs: sh2, sh3, ptb, ph (don't need to know these) |
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| accounts for signaling by such diverse molecules as interferons, GH, prolactin, Egf... receptor binds to jak, which phosphorylates stat, which forms a complex of phosphorylated stat on dna. (tyrosine kinase is NOT the receptor in this one; JAK is.) |
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Definition
| small g-protein signal initiation, a cascade of 3 protein kinases, a terminal kinase that is activated upon dual phosphorylation of nearby thr and tyr residues. |
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| stimuli: growth factors, cytokines and cellular stress, just cellular stress (induce what effects?) |
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Definition
| gf> growth stimulation, ccs> growth stimulation or stress response, cs> growth inhibition stress response |
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| non-receptor kinase: Src. |
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| tyrosine phosphorylation is central to |
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| mutation causes short stature and impaired immune function |
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| alpha and beta subunits of insulin receptor... |
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Definition
| have extracellular domains and are glycosylated. beta spans the membrane and is a protein tyrosine kinase with multiple autophosphorylation sites; alpha has a cysteine rich domain involved in insulin binding. |
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Definition
| the best characterized protein that is phosphorylated on tyrosine in response to insulin. it is a DOCKING protein with multiple SH domains. upon tyrosine phosphorylation, it serves as a binding site for other signaling proteins, which leads to activation of a signal transduction complex. |
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| how does insulin affect serum glucose concentration |
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Definition
| in liver, inhibits gluconeogenesis. in muscles, promotes glucose disposal by stimulating glucose uptake |
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| increase in skeletal muscle glucose disposal affects Km or Vmax or both? what does this imply? |
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Definition
| Vmax, which implies that stimulation of glucose transport depends on an increase in transport number |
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Definition
| used to show that insulin activates glucose transport by increasing the number of cell glucose receptors instead of activating the ones that are already there. this is accomplished by translocation of transporters from intracellular membranes |
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Term
| erythroid transporter, glut4 |
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Definition
| glut4 potently translocated in response to insulin; ET to a lesser degree. |
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| brain, pancreatic beta cells, liver transporters |
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| key catabolic enzymes are often _ by insulin. enzymes activated by insulin are _. most of insulin's effects result from _ of regulatory enzymes. |
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Definition
| inactivated, anabolic, dephosphorylation |
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Definition
| accounts for dephosphorylation of PFK2, ACC, etc. in response to insulin |
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Definition
| adult onset. impaired skeletal muscle glucose transport = hyperglycemia. |
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| insulin signaling is initiated by activation of |
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Definition
| the insulin receptor tyrosine kinase |
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Definition
| drug that prevents cancer via 1. preventing cleavage of extracellular binding domain from signal-transduction pathways, blocking dimerization of PYs, activating antibodies, promoting endocytosis of cancer causing receptors (viruses) |
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| when GTP binds (after nucleotide exchange) |
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