Problem 18
Signaling proteins, including protein kinases, often have intrinsically disordered regions (IDRs) that are important in signaling. Describe a case in which IDRs and their interactions with other proteins are important in signaling.
Problem 19
Place these events in the order in which they occur after a presynaptic neuron releases acetylcholine into the synaptic cleft. a. Vesicles containing a neurotransmitter fuse with the cell membrane. b. Ligand-gated \(\mathrm{Na}^{+}\)channels open, causing an influx of \(\mathrm{Na}^{+}\)ions. c. Voltage-gated \(\mathrm{Na}^{+}\)channels open in the axon. d. Membrane depolarization triggers voltage-gated \(\mathrm{Ca}^{2+}\) channels to open. e. Local membrane depolarization in the axon triggers an efflux of \(\mathrm{K}^{+}\).
Problem 20
The sensations of heat and cold are transduced by a group of temperature-gated cation channels. For example, TRPV1, TRPV3, and TRPM8 are usually closed, but they open at different temperatures. TRPV1 opens at \(\geq 43{ }^{\circ} \mathrm{C}\), TRPV 3 opens at \(\geq 33{ }^{\circ} \mathrm{C}\), and TRPM8 opens at \(<25^{\circ} \mathrm{C}\). These channel proteins are expressed in sensory neurons known to be responsible for temperature sensation. a. Propose a reasonable model to explain how exposing a sensory neuron containing TRPV1 to high temperature leads to a sensation of heat. b. Capsaicin, one of the active ingredients in "hot" peppers, is an agonist of TRPV1. Capsaicin shows \(50 \%\) activation of the TRPV1 response at a concentration of \(32 \mathrm{~nm}-\) a property known as \(\mathrm{EC}_{50}\). Explain why even a very few drops of hot pepper sauce can taste very "hot" without actually burning you. c. Menthol, one of the active ingredients in mint, is an agonist of TRPM8 \(\left(\mathrm{EC}_{50}=30 \mu \mathrm{M}\right)\) and TRPV3 \(\left(\mathrm{EC}_{50}=20 \mathrm{mM}\right)\). What sensation would you expect from contact with low levels of menthol? With high levels?
Problem 21
For each of the situations listed, provide a plausible explanation for how it could lead to unrestricted cell division. a. Colon cancer cells often contain mutations in the gene encoding the prostaglandin \(\mathrm{E}_{2}\) receptor. \(\mathrm{PGE}_{2}\) is a growth factor required for the division of cells in the gastrointestinal tract. b. Kaposi sarcoma, a common tumor in people with untreated AIDS, is caused by a virus carrying a gene for a protein similar to the chemokine receptors CXCR1 and CXCR2. Chemokines are cell-specific growth factors. c. Adenovirus, a tumor virus, carries a gene for the protein E1A, which binds to the retinoblastoma protein, pRb. (Hint: See Fig, 12-40.) d. An important feature of many oncogenes and tumor suppressor genes is their cell-type specificity. For example, mutations in the \(\mathrm{PGE}_{2}\) receptor are not typically found in lung tumors. Explain this observation. (Note that \(\mathrm{PGE}_{2}\) acts through a GPCR in the plasma membrane.)
Problem 22
Explain why mutations in tumor suppressor genes are recessive (both copies of the gene must be defective for the regulation of cell division to be defective), whereas mutations in oncogenes are dominant.
Problem 23
Explain why some children with retinoblastoma develop multiple tumors of the retina in both eyes, whereas others have a single tumor in only one eye.
Problem 24
Discuss the validity of the proposition that a signaling molecule (hormone, growth factor, or neurotransmitter) elicits identical responses in different types of target cells if those cells contain identical receptors.
