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What is the purpose of A kinase–associated proteins (AKAPs)? Describe how AKAPs work in heart muscle cells.
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- Describe the protein kinase cascade stimulated by epinephrine in liver cells or by insulin in muscle cells. How can it go wrong? What happens if it goes wrong? Explain the usefulness of protein kinase cascades and mechanisms to shut them down. Please give explanations for every step of this pathway. Define all technical terms you use.What is the mechanism by which R subunits inhibit the C subunits in protein kinase A?What are the primary structures of the 1AWJ tyrosine kinase enzyme? What are the secondary structures of the 1AWJ tyrosine kinase enzyme? What is the property of tyrosine kinase enzymes?
- What is the function of a protein kinase? What amino acids are often phosphorylated by kinases?Mutant tyrosine kinase signaling proteins are implicated in many types of human cancer. Hundreds of millions of dollars are required for the basic research and development of a new drug. Tyrosine kinase inhibitor drugs have been approved for cancer treatments by the U.S. Food and Drug Administration. What do you think would be some of the difficulties of finding these drugs given that similar kinases are active in normal cells? Do you think new medications of this type should be developed through government-sponsored research? Why or why not? If not, what alternatives do you propose?Identify eight general types of protein kinases found in eukaryotic cells, and explain what factor is directly responsible for activating each type.
- GTP binding proteins are molecular switches. How do GTP binding proteins work? Provide two examples of GTP binding proteins that function in intracellular protein transport. Make a drawing that illustrates the function of each of these proteins in their respective roles. Predict the direct outcome of a mutation that: Inhibits GTPase activity Inhibits interaction with the GEFCompare the three kinases - PKA, PKC, and CaMKinase II in terms of activation. What is the initial signal that activates them, what components are part of the kinase, and how does the structure modify when activated?What amino acid residue gets phosphorylated on the Receptor Tyrosine Kinase protein?
- What would be the effect of inhibiting the kinase?Suppose that Protein J which is a hypothetical protein kinase receptor was determined to be related to the progression of cancer through its activation. It was also determined that the protein exists in the active and inactive forms. The said active form is highly similar to the Protein K's conformation. Ligands A, B, and C, which are lead inhibitor compounds, were optimized to inhibit Protein J. The affinities of the ligands are shown in the table. Kp values Active Protein J Inactive Protein J Protein K Ligand A 10 mM 20 nM 5 mM Ligand B 20 nM 10 mM 15 nM Ligand C 20 nM 15 nM 15 nM Question: a. Which of the ligands, based on the table, has the highest specificity in binding to the target Protein J?Suppose that Protein J which is a hypothetical protein kinase receptor was determined to be related to the progression of cancer through its activation. It was also determined that the protein exists in the active and inactive forms. The said active form is highly similar to the Protein K's conformation. Ligands A, B, and C, which are lead inhibitor compounds, were optimized to inhibit Protein J. The affinities of the ligands are shown in the table. Kp values Active Protein J Inactive Protein J Protein K Ligand A 10 mM 20 nM 5 mM Ligand B 20 nM 10 mM 15 nM Ligand C 20 nM 15 nM 15 nM Question: a. Which of the ligands, based on the table, may be expected to be the most potent or have the highest activity against cancer? Explain. b. Which of the ligands, based on the table, may be expected to be least toxic to normal cells? Explain.