Place the following insulin signaling transduction events in o...

Question

Place the following insulin signaling transduction events in order of occurrence (event 9 is provided).

a) Full activation of PKB/Akt ______.

b) Activated PI3K converts PIP₂ to PIP₃ ______.

c) GLUT4 expressed in the cell membrane ___9___.

d) Ligand/insulin binding to the insulin receptor ______.

e) GSK3 is phosphorylated & inactivated ______.

f) Activated PDK1 phosphorylates & activates of PKB/Akt ______.

g) IRS-1 is phosphorylated & activated by the insulin receptor ______.

h) Autophosphorylation of the insulin receptor ______.

i) PI3K is activated upon its SH2 domain binding phosphorylated IRS-1 ______.

j) Glycogen synthase converts glucose to glycogen ______.

k) PIP₃ molecules laterally diffuse to bind PKB/Akt & PDK1 ______.

Accepted Answer

Alright. So here we have a practice problem that's really testing our memories of the insulin signaling pathway on glucose metabolism. And it's asking us to place the following insulin signaling transduction events that we see down below right here in order of occurrence, and it tells us that event 9 is already provided for us as you can see right here. And so, of course, we're going to need to recall a lot of information from our previous lesson videos. And so, for this particular practice problem, I would encourage you to actually go back to our previous lesson videos and your previous notes to answer this practice problem. And as we move forward in our course, we're actually going to share with you guys an interesting memory tool to help you answer practice problems like this one. But for now, you can go ahead and use your notes to help you answer this problem. And so, of course, the very first event that's going to take place in insulin signaling transduction is that the ligand, which is of course going to be insulin, is going to bind to the insulin receptor. And so that's pretty much how all biosignalling pathways start with the ligand binding to the receptor. So this will be our step number 1. Now moving on, of course, after the ligand binds the insulin receptor, because the insulin receptor is a receptor tyrosine kinase or an RTK, that is going to trigger the autophosphorylation of the insulin receptor. And so, that will be, step number 2 here. And the autophosphorylation of the insulin receptor fully activates the insulin receptor's Tyrosine Kinase domains and that allows it to, target its substrate, the insulin receptor substrate 1 or IRS 1. And so, the insulin receptor substrate 1 is going to be phosphorylated and activated by the insulin receptor, and really that will be our step 3. And then, of course, the enzyme referred to as phosphoenosetide 3 kinase or p I three k is going to get activated by IRS 1 upon its s h two domain binding to the phosphorylated IRS 1. So this will be our step number 4. And again, p I three k is phosphoenosetide 3 kinase. So it's a kinase, so we expect it to phosphorylate its substrate. And more specifically, its substrate is going to be PIP 2. And so, notice that our step number 5 is gonna be that this activated p I three k is going to convert its substrate PIP 2 into PIP 3, again phosphorylating PIP 2 into PIP 3. And so, again, this will be our step number 5. And then, of course, upon the generation of PIP 3, the PIP 3 molecules are going to laterally diffuse to bind to the enzyme protein kinase b, which in some of your textbooks is referred to as AKT. So, p k b and AKT are referring to the same thing. And also PIP 3 molecules will also diffuse and bind to the enzyme PIP 3 dependent kinase 1 or PDK 1. And so this will be our step number 6. And then, of course, that means that our step number 7 is that this PDK 1 enzyme is going to be activated. And because it is a PIP 3 dependent kinase, it is a kinase, so it's going to phosphorylate its substrate and its substrate is actually p k b. And so in step 7, what we expect is that this activated pdk 1, because again it is a kinase, it's going to phosphorylate and activate its substrate which is again p k b or a k t. So this will be our step number 7. And then of course, the phosphorylation and the activation of p k b or a k t, is gonna lead to its full activation. And so we have now full activation of pkb or AKT and that will be our step number 8. And then of course, we know that pkb is a protein kinase b, so it's another kinase. And so it's also going to phosphorylate its substrates, a bunch of different targets. And of course, step number 9 here was already given to us. So some of those targets that PKB is going to phosphorylate will ultimately lead to step number 9, which is that GLUT 4 is going to get expressed in the cell membrane, and that allows the cells to bring in the blood glucose into the cell and decrease blood glucose concentration. And so notice that we only have 2 steps here that are remaining, and notice that step e here says g s k 3 is phosphorylated and inactivated. And recall, g s k 3 is Glycogen Synthase Kinase 3, and so this is a kinase that regulates the activity of Glycogen Synthase, and normally GSK 3 will inactivate Glycogen Synthase. However, upon full activation of p k b, GSK 3 is actually going to get phosphorylated and inactivated by pkb. And so this will actually be our step number 10 here since, again, step number 9 was already taken by this. And then, of course, that means that our last step down below here, is gonna be our final step, and that is that, now that g s k 3 has been phosphorylated and inactivated, it can no longer inactivate glycogen synthase. And so glycogen synthase is now free to convert glucose into glycogen, and that is the step number 11. And so really all of the numbers that you see here are the answers to this practice problem and this is the correct order of events. And so, that concludes this practice. And again, as we move forward in our course, we're going to share with you guys some helpful memory tools to help you guys, memorize these steps, the most important steps of this pathway. So that concludes this practice problem and I'll see you guys in our next video.

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