Your friend is studying mouse fur color and has isolated the GPCR responsible fo
ID: 93050 • Letter: Y
Question
Your friend is studying mouse fur color and has isolated the GPCR responsible for determining its color, as well as the extracellular signal that activates the receptor. She finds that, on addition of the signal to pigment cells (cells that produce the pigment determining fur color), cAMP levels rise in the cell. She starts a biotech company, and the company isolates more components of the signaling pathway responsible for fur color. Using transgenic mouse technology, the company genetically engineers mice that are defective in various proteins involved in determining fur color. The company obtains the following results. Normal mice have beige (very light brown) fur color. Mice lacking the extracellular signal have white fur. Mice lacking the GPCR have white fur. Mice lacking cAMP phosphodiesterase have dark brown fur. Your friend has also made mice that are defective in the alpha subunit of the G protein in this signaling pathway. The defective alpha subunit works normally except that, once it binds GTP, it cannot hydrolyze GTP to GDP. What color do you predict that the fur of these mice will be? Why? A certain mutation in the receptor for epidermal growth factor (EGF) causes the mutated receptor protein to send a positive signal along the associated intracellular signaling pathway even when the EGF ligand is not bound to it. This signal leads to abnormal cell proliferation in the absence of growth factor. On the basis of this information, would you class the gene for the EGF receptor as a tumor suppressor gene or a potential oncogene? Explain your answer.Explanation / Answer
Answer:
7. Mice with defective G alpha should have white fur. The data presented above suggests that a lack of extracellular signal or defective GPCR results in white fur due to a block in the signaling events. Since the G protein can bind to GTP but cannot hydrolyze it to GDP, the signal is blocked, resulting in white fur color.
Expression of some synthetic pigments may become constitutive if the regulation of the signal is faulty, as in case of cAMP phosphodiesterase. This results in dark brown fur.
8. The mutation discussed in the question produces a hyperactive gene product and leads to an abnormal cell proliferation. So, the gene for the EGF receptor can be classified as an oncogene.
The mutation is dominant and its effect can be seen even with a single copy of the mutated gene. Mutations that cause a deletion of the EGF gene would have either no effect on cell division or an inhibitory effect. Thus, it can be classified as a potential oncogene.
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