Can someone please answer the questions in the photo, given the diagram? 10. Sho
ID: 56968 • Letter: C
Question
Can someone please answer the questions in the photo, given the diagram? 10. Shown below is the signaling pathway of the insulin receptor, which uses similar principles but different molecular elements than a prototypical GPCR signaling pathway. Activation of the signaling pathway after insulin binding involves cross-phosphorylation by each monomer of the dimer at several sites, which then act as binding sites for phosphorylated insulin-receptor substrate (IRS-1). Phosphoinositide-3-kinase then binds to phosphorylated sites on IRS-1 through its regulatory domain, then converts PIP2 into PIP3. Binding to PIP3 activates PIP3-dependent protein kinase, which phosphorylates and activates several proteins including kinases such as Aktl. Based on the above description and your analysis of the diagram, answer the following questions Insulin receptor A) What is the primary messenger in the signaling pathway shown here? (1 pt insulin PIP2 B) Name two amplification steps in the pathway shown here (4 pts) PIP C) Name two ways of specifically turning off this signaling pathway. (4 pts) Pi, dependent protela knase Phospheinositide 3-kinase P D) Prolonged exposure to agonist ligands causes desensitization of GPCRs. Briefly describe how GPCR are desensitized? (2 pts) ATP ADP Akt Activated Akt E) In an interesting experiment, scientists studying this desensitization phenomenon noticed that addition of a protein phosphatase to the signal transduction pathway caused resensitization of the GPCR. Based on what you know about desensitization mechanism in GPCRs, explain this observation (2 pts)
Explanation / Answer
1. Insulin
2. a. Multiple phosphoIRS1 binding sites are there on a single Receptor Tyrosine Kinase Dimer amplifying the response
b. PIP3 Dependent Protein Kinase (PDK1) amplifies the response by activating many downstream molecules like Akt via phosphorylation.
3. a. Preventing Insulin receptor dimerization by mutating the dimerization domain.
b. Mutating regulatory domain of PI3K so that it does not recognise PhosphoIRS.
4. GPCRs are desensitized based on feedback inhibition by cAMP based kinases or special GPCRkinases, which phosphorylate the receptor at inhibitory sites, and after prolonged activation, changes its nature from G(stimulatory) to G(inhibitory)
5. After the receptor is desensitized by inhibitor phosphorylation, the phosphatase cleaves the inhibitory phosphate, resensitizing the receptor.