Homework Practice Problems Review Session 9 28 23 Answer KEY EGF signaling causes cell division one of the hallmarks of cancer Which of the following could represent a mutation in the EGF pathway that could lead to extra signaling and increase cell division and contribute to cancer T1 EGF receptor kinase activity could be on even if no EGF signal was present T2 Overexpression of EGFR could induce dimerization and activation even if no EGF signal was present T3 Ras GEF activity could be constantly on F4 Ras GAP activity could be constantly on F5 Ras GTPase activity could be on even without GAP activity T6 Ras GTPase activity could be blocked even with GAP activity T7 RAF kinase activity could be activated without contact with GTP bound Ras T8 The rate of Ubiquitin dependent proteolysis of MEK could be decreased T9 MEK could mutate to mimic phosphorylation activating kinase without actual phosphorylation T10 ERK could enter the nucleus and phosphorylate transcription factors even though it is not itself phosphorylated You analyze a cell expressing the EGF signaling pathway and nd the following The receptors are not dimerized The Ras GEF is not active ERK is in the nucleus phosphorylating transcription factors Which of the following could account for these results T1 There could be a mutation in RAF that activates its kinase domain F2 There could be a mutation in RAS the blocks its GTPase activity NOTE Because Ras GEF is not active Ras would be in its GDP bound state and GTPase activity only matters if Ras is binding GTP Bloc F3 There could be a mutation in the RAS GAP that blocks its function T4 There could be mutation in MEK that activates its kinase domain F5 There could be a mutation that causes overexprssion of the HER2 version of the EGF receptor You analyze a cell expressing the normal EGF pathway and nd that ERK is in the nucleus actively phosphorylating transcription factors What else would expect to be true T1 The EGF receptor subunits would be dimerized T2 The RAS GEF should be active T3 The RAS GAP would be active NOTE In the normal EGF pathway Ras is turned on and back o constantly kind of like protein turnover T4 The RAF RBD Ras binding domain would be in contact with RAS F5 RAF would be phosphorylated T6 MEK would be phosphorylated A loss of function mutation in Ras causes it to lose its GTPase activity Which of the following drugs could still block the EGF pathway when this Ras mutation is present Assume EGF signal is constantly present F1 Herceptin Blocks EGF from binding to receptor F2 Tarceva Blocks Kinase activity of receptor T3 Vemurafenib Blocks Raf Kinase activity T4 Selumetinib Blocks MEK Kinase activity T5 EPE Protein Prevents ERK from entering the nucleus F6 All of these drugs would block EGF signaling HER2 can dimerize with EGFR or HER3 requires EGF signal HER2 can dimerize with itself and does not require EGF signal HER2 overexpression is common in some cancers HER2 can dimerize with itself or with other members of the EGFR family HER2 does not bind to EGF but can dimerize anyhow HER1 must bind to EGF to dimerize with itself or HER2 How could HER2 overexprssion contribute to cancer T1 HER2 overexpression could create activated EGFR dimers even when little EGF signal was present T2 HER2 overexpression would create activated EGFR dimers even when no EGF signal is present You analyze a cell receiving the adrenaline signal and nd the following G protein alpha is binding GTP The regulatory subunits of PKA are not binding the kinase subunit of PKA Monoamine oxidase is functioning outside the cell If the signaling pathway was functioning normally what else should be true 1 Adrenaline has been binding to the receptor 2 Phosphodiesterase has converted all the cAMP into AMP 3 CREB should be phosphorylated 4 Adrenaline concentrations outside the cell should be decreasing See edited question on next slide You analyze a cell that is recovering after receiving the adrenaline signal and nd the following G protein alpha is binding GTP The regulatory subunits of PKA are not binding the kinase subunit of PKA Monoamine oxidase is functioning outside the cell If the signaling pathway was functioning normally what is true about this cell 1 The amount of Adrenaline binding to the receptor is decreasing 2 Phosphodiesterase is converting cAMP into AMP 3 CREB is phosphorylated 4 Adrenaline concentrations outside the cell are decreasing Some people scare easily and stay upset from a frightening experience for a long time Which of the following could make people over sensitive to adrenaline response to fright and or slow to recover T1 They could have chronically low levels of Monoamine Oxidase F2 They could have high levels of G protein alpha GAP T3 They could have low levels of phosphodiesterase F4 They could have high levels of phosphatase that target CREB