UMass Amherst BIOLOGY 285 - Bio 285 Review Exam 2 (3 pages)

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Bio 285 Review Exam 2



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Bio 285 Review Exam 2

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3
School:
University of Massachusetts Amherst
Course:
Biology 285 - Cellular & Molecular Biology
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Bio 285 Exam 2 Review Laura Allostery a molecule that binds an enzyme somewhere other than the active site and controls the enzyme s function o To regulate activity o Causes enzyme to change shape activity Mechanism of enzyme function stuff mechanism of protein regulation stuff should know for exam basically memorize slides Memorize pathways for exam Q What makes it an active site o Enzyme is a molecule usually a protein that catalyzes a chemical reaction active site defined as where substrate binds where chemical reaction occurs o Binding to somewhere other than the active site changes enzyme shape affects ability to bind substrates change ability to catalyze chemical reaction have to be in active site to catalyze chemical reaction Q intrinsic kinase activity vs extrinsic kinase activity o Intrinsic kinase activity of thing you re talking about its own kinase activity o Extrinsic kinase activity of another molecule Autophosphorylation increases intrinsic kinase activity Wildtype Abl kinase may dimerize autophosphorylate don t run around the cell as dimers o Bcr gives them capability to tetramerize or polymerize brings two relations in close to each other and that cross phosphorylation activates that kinase activity Know parts of Abl skip Bcr Abl stuff how does Abl control itself autoinhibitory function how regulated Ras GEF GAP stuff should know Ras mutations cause cancer Ran mutations do not o Ras and Ran structurally related but who Ran and Ras bind to are different o Ran GEF GAP different from Ras GEF GAP o Essentially molecular switches o Ras GDP bound state molecular switch things to be regulated in cell Q compare contrast Ras G proteins o Less related Bad s function is to inhibit Bcl2 o For survival of cells want Bad to be off o But sometimes cell survival is not right thing sometimes cell should be activating programmed cell death pathways Not having programmed cell death not regulating it correctly can be not good o Bad s function is to bind Bcl2 then undergo cell death o Bcl2 s job is to inhibit programmed cell death when active o Bcl2 binds to something on mitochondria when it s doing its job Actively inhibits cell death o Bad tries to pull Bcl2 off mitochondria sequester it Then becomes inactive o Bad Bcl2 programmed cell death happening o Bcl2 alone programmed cell death not happening o Active AKT programmed cell death not happening b c AKT phosphorylating Bad which can t bind Bcl2 o When AKT active Bad is inactive When protein phosphorylated protein is inactive in this case o AKT must be phosphorylated twice at two different sites active state when phosphorylated Sequential phosphorylation o Kinase active in cell cycle kinase active later in cell cycle o First kinase must be phosphorylated for second kinase to be phosphorylated o Might be happening to Abl o First site opens up possibility for second site Q does AKT need to be bound to PIP3 o Phosphorylated by two different kinases that s good enough o Does one of protein kinases need to be bound to PIP3 too Yes one anchored at PIP3 and one soluble Q if protein kinase 1 isn t working could protein kinase 2 phosphorylate AKT o PK1 is dependent upon PK2 o 1 needs to phosphorylate first then active site opens for 2 o Sequential Survival signaling dimerization pip2 pip3 etc Q how do proteins bind to PIP3 o PH PTEN o Takes phosphate off PIP3 and gives back to PIP2 o Tumor suppressor o LOF in PTEN make pathway too active survival pathway so making them too active leads to cancer Q overall picture in inhibiting apoptosis survival signal transduction and cancer how do they relate o Cells with cancer often find LOF in proteins that lead to programmed cell death o Overall survival pathways are functioning too well programmed cell death pathways aren t working well enough o Pathways that lead to programmed cell death broken in some way Q RTK pathway leads to the inhibition of apoptosis so if too active that leads to cancer o Contributing factor o Lots of ways to break pathways o Having overdivision pathway o Having broken DNA damage response pathways o PIP3 major regulator of response of bad things happening in cell break that can t respond normally to cell damage o Which aspects of this pathway would lead to cancers Anything that causes survival to happen when it shouldn t happen Q question 12 on practice q s LOF Ras GAP What would happen o Ras would be bound to GTP all the time o Any part of pathway that wouldn t transduce signal Problem with this Couldn t turn it off potentially oncogenic o Ras still binding to RTK no Go over JAX STAT pathway o Signal that causes receptor dimerization o Receptor itself in JAX STAT has no enzymatic activity just brings this together o JAK1 and JAK2 have enzymatic activity noncovalently bound to the receptor o When JAK1 and JAK2 brought into close proximity to each other b c signal binds so dimerizes JAX are nonreceptor tyrosine kinases Nonreceptor tyrosine kinases are soluble tyrosine kinases who can float around cell o JAK1 and JAK2 will phosphorylate each other activate each other when close dimerization brings them close o Then activate downstream proteins o Once JAX are active they phosphorylate each other and then phosphorylate the receptor o That creates binding sites for the STATs Means STATs probably have a SH2 domain STAT comes and binds gets phosphorylated by GAPs causes them to change shape then dissociate from where on receptor and then STAT1 and STAT2 come together dimerize and they go into the nucleus and activate transcription STATs are transcription factors Bcr Abl not necessary to know for exam Background on CML pathology not necessary to be memorized Q why does nonfunctional SH2 domain lead to activation of Abl o Could argue SH2 either way o SH2 could play important roles in downstream signaling for Abl but also could play important autoinhibitory role o Get rid of SH2 potentially have overactive kinase Go back and reread Abl review on Perusall Abl autoinhibition o CAP where myristate is bound SH2 SH3 linker forms intramolecular interactions inhibited state o Survival cytoplasmic cell mobility cytoplasmic DNA damage response nuclear DNA binding domain DNA damage response Actin binding domain o Proliferation Bcr Abl more able to signal in proliferation pathways Abl functions in a number of different pathways Q do STATs have SH2 domains o Yes Q what s a chimera o Bcr Abl is example Q flexible homology o Different kind of binding domain Q Who regulates who in Bad Bcl2 What


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