Lecture 22 Flashcards
Cell Signaling Questions
A 45-year-old woman with a body mass index (BMI) of 32 kg/m² is struggling with obesity and is started on semaglutide, a GLP-1 receptor agonist. After several weeks of treatment, she experiences weight loss and improvements in her glycemic control. Which of the following best describes the mechanism by which semaglutide exerts its effects through signaling?
A) Activation of phospholipase C, leading to increased intracellular calcium levels and enhanced satiety signaling in the hypothalamus
B) Stimulation of adenylate cyclase, resulting in increased cyclic AMP levels, which promotes insulin secretion and reduces appetite
C) Binding to the GLP-1 receptor, activating Gs proteins, which stimulates adenylate cyclase and increases cyclic AMP levels in pancreatic beta cells and neurons
D) Inhibition of the reuptake of serotonin, leading to enhanced mood and appetite suppression through 5-HT receptors
E) Activation of Gq proteins, leading to increased phosphatidylinositol turnover and enhanced energy expenditure
C) Binding to the GLP-1 receptor, activating Gs proteins, which stimulates adenylate cyclase and increases cyclic AMP levels in pancreatic beta cells and neurons
Semaglutide is a GLP-1 receptor agonist that mimics the action of the incretin hormone GLP-1. When semaglutide binds to the GLP-1 receptor, which is a G-protein coupled receptor, it activates Gs proteins. This activation stimulates adenylate cyclase, leading to an increase in cyclic AMP (cAMP) levels in pancreatic beta cells. The elevated cAMP enhances insulin secretion in response to glucose, promotes satiety, and reduces appetite by acting on neurons in the hypothalamus. These combined effects contribute to weight loss and improved glycemic control in individuals with obesity.
A 50-year-old man presents to a sleep clinic with chronic insomnia characterized by difficulty initiating and maintaining sleep. After a thorough evaluation, he is prescribed an orexin receptor antagonist to help improve his sleep quality. The mechanism of action of this medication is based on its effects on the hypothalamic orexin system. Which of the following best describes the signaling mechanism by which orexin receptor antagonists exert their therapeutic effects in the treatment of insomnia?
A) Inhibition of adenylate cyclase, leading to decreased cyclic AMP levels and subsequent sedation through G protein-coupled receptor signaling
B) Competitive blockade of orexin 1 (OX1) and orexin 2 (OX2) receptors, preventing Gq protein activation, which reduces phospholipase C activity and subsequent calcium mobilization in wake-promoting neurons
C) Activation of Gq protein signaling, resulting in increased phospholipase C activity and enhanced intracellular calcium levels to induce sleep
D) Stimulation of GABA receptors, leading to increased inhibitory neurotransmission and enhancement of sleep quality
E) Modulation of serotonin reuptake, resulting in increased serotonin levels that promote sleep induction
B) Competitive blockade of orexin 1 (OX1) and orexin 2 (OX2) receptors, preventing Gq protein activation, which reduces phospholipase C activity and subsequent calcium mobilization in wake-promoting neurons
Orexin receptor antagonists work by competitively blocking orexin 1 (OX1) and orexin 2 (OX2) receptors, which are coupled to Gq proteins. This blockade prevents Gq protein activation, leading to a decrease in phospholipase C activity and a reduction in intracellular calcium mobilization in wake-promoting neurons located in the lateral hypothalamus. As a result, the excitatory signaling that promotes wakefulness is diminished, facilitating the onset and maintenance of sleep. Other options describe mechanisms that do not accurately reflect the action of orexin receptor antagonists.
A 60-year-old woman presents to the oncology clinic with newly diagnosed HER2-positive breast cancer. She reports persistent fatigue, weight loss, and a firm, palpable mass in her right breast. A mammogram reveals a 4 cm tumor with associated lymphadenopathy in the right axilla. Immunohistochemical analysis confirms overexpression of the HER2 protein. The oncologist discusses initiating treatment with trastuzumab.
Which of the following best describes the mechanism of action of trastuzumab in treating HER2-positive breast cancer?
A) Trastuzumab binds to the extracellular domain of the HER2 receptor, preventing its dimerization and subsequent activation of the PI3K/AKT and MAPK signaling pathways.
B) Trastuzumab activates the HER2 receptor, leading to enhanced signaling through the JAK-STAT pathway and promoting cell proliferation.
C) Trastuzumab induces apoptosis by directly activating caspase-3 through interaction with the intracellular domain of the HER2 receptor.
D) Trastuzumab inhibits angiogenesis by blocking the interaction between HER2 and vascular endothelial growth factor (VEGF).
E) Trastuzumab enhances T-cell-mediated cytotoxicity by binding to the HER2 receptor and recruiting immune effector cells through antibody-dependent cellular cytotoxicity (ADCC).
A) Trastuzumab binds to the extracellular domain of the HER2 receptor, preventing its dimerization and subsequent activation of the PI3K/AKT and MAPK signaling pathways.
A 55-year-old woman presents to the oncology clinic with recurrent HER2-positive breast cancer. She reports increasing fatigue, weight loss, and intermittent bone pain over the past month. Imaging studies reveal multiple metastatic lesions in the bones and lungs, as well as a 3 cm mass in her left breast. Previous treatment included surgery, chemotherapy, and trastuzumab. The oncologist discusses the addition of pertuzumab to her treatment regimen.
Which of the following best describes the mechanism of action of pertuzumab in the management of HER2-positive breast
cancer?
A) Pertuzumab binds to the intracellular domain of HER2, preventing activation of the MAPK and PI3K/AKT pathways.
B) Pertuzumab inhibits HER2 receptor recycling, leading to prolonged receptor degradation and decreased signaling.
C) Pertuzumab binds to the dimerization arm of the HER2 receptor, preventing heterodimerization with HER3 and blocking downstream signaling pathways.
D) Pertuzumab activates immune effector cells through antibody-dependent cellular cytotoxicity (ADCC), leading to enhanced tumor cell lysis.
E) Pertuzumab inhibits angiogenesis by disrupting the interaction between HER2 and vascular endothelial growth factor (VEGF).
C) Pertuzumab binds to the dimerization arm of the HER2 receptor, preventing heterodimerization with HER3 and blocking downstream signaling pathways.
A 62-year-old man presents to the oncology clinic with fatigue, weight loss, and abdominal pain. Imaging reveals a large mass in the pancreas, and biopsy confirms pancreatic adenocarcinoma. Molecular analysis shows a mutation in the KRAS gene, leading to continuous activation of the RAS signaling pathway. The oncologist discusses the role of RAS in cancer and the potential therapeutic strategies targeting this pathway.
Which of the following best describes the mechanism by which GTPase-activating proteins (GAPs) regulate RAS signaling in the context of cancer?
A) GAPs enhance the exchange of GDP for GTP on RAS, promoting its active GTP-bound form and increasing downstream signaling.
B) GAPs facilitate the hydrolysis of GTP to GDP on RAS, thereby inactivating RAS and reducing its signaling activity.
C) GAPs directly phosphorylate RAS, enhancing its interaction with downstream effectors such as RAF and PI3K.
D) GAPs bind to the active form of RAS, preventing its interaction with downstream signaling molecules and inhibiting proliferation.
E) GAPs increase the expression of RAS, leading to enhanced signaling through the MAPK and PI3K pathways.
B) GAPs facilitate the hydrolysis of GTP to GDP on RAS, thereby inactivating RAS and reducing its signaling activity.
A 68-year-old woman presents to the oncology clinic with a diagnosis of metastatic colorectal cancer. She reports significant weight loss, intermittent abdominal pain, and changes in bowel habits. Imaging studies show multiple liver metastases, and a biopsy confirms the diagnosis. The oncologist discusses initiating treatment with bevacizumab as part of her therapeutic regimen.
Which of the following best describes the mechanism of action of bevacizumab in the management of cancer?
A) Bevacizumab binds to and activates the vascular endothelial growth factor (VEGF) receptor, promoting angiogenesis and enhancing tumor blood supply.
B) Bevacizumab inhibits the binding of VEGF to its receptor, thereby preventing angiogenesis and reducing tumor vascularization.
C) Bevacizumab stimulates the production of anti-angiogenic factors, leading to decreased endothelial cell proliferation and enhanced apoptosis of tumor cells.
D) Bevacizumab directly induces apoptosis in tumor cells by activating the caspase pathway through VEGF receptor inhibition.
E) Bevacizumab enhances T-cell-mediated anti-tumor immunity by blocking the interaction between VEGF and immune checkpoint proteins.
B) Bevacizumab inhibits the binding of VEGF to its receptor, thereby preventing angiogenesis and reducing tumor vascularization.
A 45-year-old woman presents to the clinic with fatigue, weight loss, and a palpable mass in her neck. Imaging studies reveal a thyroid nodule, and fine needle aspiration biopsy shows the presence of papillary thyroid carcinoma. Molecular analysis reveals a mutation in the RET proto-oncogene, which encodes a receptor tyrosine kinase involved in cell signaling. Which of the following best describes the mechanism of action of receptor tyrosine kinases (RTKs) in cellular signaling?
A) RTKs undergo dimerization upon ligand binding, leading to autophosphorylation of tyrosine residues on the receptor and activation of downstream signaling pathways.
B) RTKs are activated by the binding of ligands that induce conformational changes, resulting in the release of intracellular calcium ions and activation of calmodulin.
C) RTKs signal through G-proteins that activate adenylate cyclase, increasing cyclic AMP levels and promoting gene transcription.
D) RTKs are primarily involved in ligand-induced endocytosis, which leads to the degradation of signaling molecules in the lysosome.
E) RTKs directly activate nuclear transcription factors upon ligand binding, promoting rapid gene expression without the need for intermediary signaling molecules.
A) RTKs undergo dimerization upon ligand binding, leading to autophosphorylation of tyrosine residues on the receptor and activation of downstream signaling pathways.
A 28-year-old woman presents to the clinic seeking advice on medication options for terminating an early pregnancy. After a thorough discussion of her options, the physician prescribes mifepristone, explaining its mechanism of action.
Which of the following best describes the mechanism of action of mifepristone in the context of pregnancy termination?
A) Mifepristone activates receptor tyrosine kinases, promoting cellular proliferation and maintenance of the uterine lining.
B) Mifepristone binds to progesterone receptors, inhibiting their action and leading to decidual breakdown and termination of pregnancy.
C) Mifepristone stimulates G-protein coupled receptor (GPCR) signaling, increasing uterine contractions and facilitating expulsion of the pregnancy.
D) Mifepristone acts as a competitive antagonist of estrogen receptors, preventing estrogen’s effects on the uterine lining.
E) Mifepristone enhances nitric oxide signaling, leading to vasodilation and increased blood flow to the uterus.
B) Mifepristone binds to progesterone receptors, inhibiting their action and leading to decidual breakdown and termination of pregnancy.
A 37-year-old woman with no remarkable previous health history presents to the emergency department with complaints of vomiting, watery diarrhea, and dry mouth. Vitals are temperature 37 °C (98.6 °F), pulse rate 130 beats/minute, and blood pressure 80/60 mm Hg. The patient reveals that she recently traveled abroad and consumed raw oysters from a nearby lake in the village where she stayed. The patient is diagnosed as having been infected with cholera toxin. Which subunit of the G protein is affected by the action of cholera toxin?
A. G alpha
B. G beta
C. G gamma
D. G inhibitor
A. G alpha
A 59-year-old man is brought to the emergency department after losing consciousness while walking. He spontaneously regains consciousness after 15 seconds. His past medical history includes atrial fibrillation, for which he is taking a medication that blocks receptors. He took double the dose of his medication today because he forgot to take it yesterday.
Which of the following is the most likely cause of his syncope?
A.Decreased activity of protein kinase C in cardiomyocyte
B.Decreased activity of adenylyl cyclase in cardiomyocytes
C.Decreased activity of adenylyl cyclase in vascular smooth muscle cells
D.Decreased diastolic efflux of calcium in cardiomyocytes
B.Decreased activity of adenylyl cyclase in cardiomyocytes
