So here we're going to briefly revisit our map of the lesson on biosignalling pathways, which is down below right here. And, of course, we know that we've been exploring this map by exploring the leftmost branches first, and so we're currently talking about G protein coupled receptors. And we've already covered the adenylate cyclase GPCR signaling pathway in terms of the stimulatory pathway, which involves cAMP and PKA. And we've also covered the inhibitory pathway as well as drugs and toxins that affect GPCR signaling. And we're currently exploring the phosphoenosatide GPCR signaling pathway. And so now that we've introduced this phosphoenosatide GPCR signaling pathway, in this video, we're going to continue to talk about the phosphoenosatide GPCR signaling pathway as we talk more details about the secondary messengers such as IP3 and DAG, calcium and calmodulin, and also, the enzymes protein kinase C. And so let's go on and get started talking about these particular molecules. So here we're going to continue to talk about the phosphoenosatide signaling pathway or PSP. And more specifically, we're going to focus on the PSP secondary messengers and protein kinase C or PKC. Now in this video specifically, we're going to focus on the secondary messengers, IP3 and DAG. And so recall from our previous lesson videos that upon activation of the effector enzyme protein Lipase C or PLC, it's actually going to catalyze the hydrolysis of the substrate called PIP2. And so PLC hydrolysis of PIP2 is going to yield 2 secondary messengers. Inositol Triphosphate or IP3, as well as Diacylglycerol or DAG. Now recall that inositol triphosphate or IP3 is going to diffuse through the cytosol to the endoplasmic reticulum surface where it's going to bind to calcium ion channels and trigger an increase in cytoplasmic calcium concentration. And so, here you can see that the cytoplasmic calcium concentration is going to increase. Now recall that diacylglycerol or DAG is not going to diffuse through the cytoplasm. Instead, it's going to remain associated with the plasma membrane. And along with the release calcium from the previous step, it's going to activate the enzyme called protein kinase C or PKC. And so if we take a look at our image down below, we can get a better visual of exactly what's happening here. And so notice over here on the far left, what we're showing you is our visual representation of the substrate PIP2. And so PIP2 again is the substrate for the effector enzyme protein like phospholipase C, which we have right here acting as the catalyst. And so, what you can see is that PLC is going to cleave, hydrolyze PIP2 into 2 secondary messengers, which you'll see down below here is going to be IP3 or inositol triphosphate. And what you see up above right here is going to be diacylglycerol or DAG. Now, of course, IP3 is going to diffuse through the cytoplasm, so there will be cytosolic diffusion, and it will diffuse all the way through the cytoplasm to reach the endoplasmic reticulum membrane. And so here you can see we're labeling it as the ER membrane where the outside here represents the cytoplasm of the cell and down here represents the inside of the endoplasmic reticulum. And notice that IP3, again, is going to diffuse through that cytoplasm until it binds to calcium ion channels embedded in the ER membrane, and it will allow them to open up so that they can release calcium from the inside of the endoplasmic reticulum and release it to the outside, here of the endoplasmic reticulum into the cytoplasm of the cell. And so this is going to lead to increased cytoplasmic calcium concentrations. And, that's important to note here. And so up above, if we take a look at what happens to diacylglycerol, notice that it is still embedded in the plasma membrane of the cell, and so it can only diffuse laterally. And so lateral diffusion is what we're showing you here, and it will diffuse laterally to activate this other enzyme over here, protein kinase C or PKC. And so diacylglycerol, along with the calcium that was released down below in this step, is going to, again, activate protein kinase C, and that activation of protein kinase C is what's going to lead or help lead to the cell response. And so now that we've got a more clear understanding of IP3 and DAG, in our next video, we're going to discuss exactly more details about the calcium and how it forms a complex with calmodulin. So I'll see you guys in our next video.
PSP Secondary Messengers & PKC - Online Tutor, Practice Problems & Exam Prep
PSP Secondary Messengers & PKC
Video transcript
PSP Secondary Messengers & PKC
Video transcript
So now that we've reviewed the 2 secondary messengers, inositol triphosphate or IP3 and diacylglycerol or DAG, in this video, we're going to focus more on the calcium ion secondary messenger and the protein calmodulin. Now calcium ions, or Ca2+, are a common intracellular signal that can trigger many different biochemical processes. Recall in our previous lesson videos, we've seen that calcium can trigger processes that include muscle contractions as well as vesicle exocytosis in neurons. However, what we have not yet mentioned in any of our previous lesson videos is that in order for calcium to affect its targets, calcium ions generally need to form a complex with another protein known as calmodulin. And so calmodulin, as you can see here, is a protein that is commonly abbreviated as just CAM in this fashion like this. And so calmodulin, or CAM, is, as its name implies, a calcium ion modulated cytosolic protein. And so you can see calcium modulated is how calmodulin's name originated. And so, calcium-modulated just means that it is calcium-dependent. And so calcium-modulated or dependent cytosolic protein, is going to activate a variety of different targets that could include protein kinases, which we know phosphorylate other targets. And so calmodulin is, again, a calcium-dependent or calcium-modulated protein. And so calmodulin is only going to be activated when all 4 of its calcium-binding sites are occupied by calcium. And so the active calmodulin calcium complex will bind to other target proteins in order to help activate, those other proteins. And so if we take a look at our image down below, notice that over here on the left what we have is a calcium ion and over here what we have is the calmodulin protein. And notice that the calmodulin protein has these 4 specific calcium binding sites. And so really, when four calcium ions bind to, calmodulin, it creates the calmodulin calcium complex that we were just discussing. And so this is the active form of the calcium calmodulin complex. And so when it is active, it can actually bind to other target proteins such as kinases like this one over here in order to help activate them. So you can see that the calcium calmodulin complex right here, again, can bind to other proteins such as this blue protein kinase over here to help activate it so that it can actually perform its function of phosphorylating other targets and helping to lead to the cell response. And so this here really concludes our introduction to calcium and calmodulin. As we move forward in our course, we'll be able to apply some of the concepts that we've learned here and some practice problems. So I'll see you guys in our next video.
PSP Secondary Messengers & PKC
Video transcript
So in this video, we're going to focus on Protein Kinase C or PKC. And, of course, we know that Protein Kinase C is commonly abbreviated as just PKC, and as its name indicates, it is indeed a kinase. So we know that it's going to be an enzyme that phosphorylates its substrates. But more specifically, Protein Kinase C or PKC is a serine threonine kinase, which means that it phosphorylates serine threonine residues on its target proteins in order to alter the activity of those target proteins, very, very similar to how the enzyme Protein Kinase A or PKA operated in our previous lesson videos. Now Protein Kinase C or PKC targets include enzymes, cytoskeletal proteins, and nuclear proteins, regulating gene expression. And so, ultimately, PKC activity can generate a wide variety of cell responses.
And so if we take a look at our image down below, notice that PKC is right here. And so when PKC is associated with DAG or diacylglycerol, as well as with calcium, then PKC takes on its active conformation. And when PKC is active, it can actually function as the kinase that it is. So it can phosphorylate its targets such as enzymes like this one, and essentially alter their activity. So notice in this particular example, it's taking an inactive enzyme, phosphorylating it here at this particular serine or threonine residue, and that ultimately alters the activity of the enzyme so that it becomes active, and then this active protein can go on to generate the cell response. But again, be careful not to associate phosphorylation with activation because phosphorylation can also sometimes lead to inactivation. And so, here we're just showing it as one particular way that phosphorylation is leading to activation. But don't forget that phosphorylation is just going to alter the activity, not necessarily lead to activation or inhibition. It will be a case by case basis.
And so this here really concludes our video on Protein Kinase C or PKC and we'll be able to get some practice applying these concepts as we move forward in our course. So I'll see you guys in our next video.
Which of the following enzymes does diacylglycerol recruit to the membrane and activate when bound?
Which of the following statements about calmodulin is TRUE?
PSP Secondary Messengers & PKC
Video transcript
In this video, we're going to talk more details about the inactivation or the termination of the phosphoenacitide GPCR signaling pathway. And so recall from our previous lesson videos that the GTPase activity in the G Protein Alpha subunit will actually participate in the inactivation or the termination of the GPCR signaling pathway to help reset the pathway. However, in addition to the GTPase activity of the G Protein Alpha Subunit, there are also 3 other events that take place that also help to inactivate or terminate the phosphoenacitide GPCR signaling pathway. And so we've got these 3 other events numbered down below in our text. The first event is that IP3 signaling effect can be turned off by decreasing the concentration of IP3 in the cell. And the cell can decrease the concentration of IP3 by using the enzyme called Inositol Polyphosphate 5 Phosphatase. This enzyme, Inositol Polyphosphate 5 Phosphatase is indeed a Phosphatase enzyme as indicated by its name. Recall that Phosphatases remove Phosphate Groups from their substrates. Inositol Polyphosphate 5 Phosphatase will remove a phosphate group from its substrate IP3, converting IP3 into IP2. IP2 does not release calcium from the reticulum like what IP3 does. When Inositol Polyphosphate 5 Phosphatase converts IP3 into IP2, it's actually helping to terminate the signal or inactivate the signal.
The second event is that PKCs or protein kinase c's activity is going to be reversed by serine threonine phosphatases as well. You can see that these phosphatases are going to play a big role in the inactivation or the termination of the signal. Phosphatases are all about removing phosphate groups from their substrates. The third event that helps to inactivate or terminate the signal is going to be that the cytoplasmic calcium concentrations, which were once increased, are now going to be decreased once again back to its original state by the enzyme sarcoplasmic endoplasmic reticulum calcium ATPase or the SERCA pump, which you might recall from our previous lesson videos is a P type ATPase. If we take a look at our image down below, we can see that we have the numbers 1, 2, and 3 here that correspond with our image above. We have the alpha subunit of the G protein dissociating and activating the effector enzyme protein lipase C, which will cleave its substrate PIP2 into DAG and IP3. IP3 goes on to open up calcium channels in the endoplasmic reticulum membrane to increase the calcium concentration in the cytoplasm. That's going to lead to calcium binding calmodulin and activating protein kinases that lead to the cell response. DAG or diacylglycerol in the plasma membrane will laterally diffuse to activate protein kinase C along with the released calcium, and protein kinase C will act as a kinase to phosphorylate its targets, leading to the cell response. In this video, again, we're focusing on the inactivation or the termination of that signal that leads to the cell response.
The first event that we talked about was the ability for Inositol Polyphosphate 5 Phosphatase to remove a phosphate group from IP3 and convert IP3 into IP2. IP2 does not open up the calcium channel in the ER membrane. This will help to terminate the signal and ensure that the cell response is not generated. The second event that we talked about was the addition of the activity of Serine Threonine Phosphatases, which will remove or reverse the activity of the kinases that we have here. The third event that will help terminate the signal is the SERCA pump, which you can see down below right here, that's helping to remove calcium from the cytoplasm and bring it right back into the endoplasmic reticulum where it originally started. These three events, along with the GTP hydrolysis of the alpha subunit, are going to lead to the inactivation or the termination of this phosphoenacitide signaling pathway. This here concludes our lesson on the inactivation or termination of phosphoenacitide GPCR signaling, and we'll be able to get some practice applying these concepts as we move forward in our course. So I'll see you guys in our next video.
Protein Kinase C (PKC) is activated when bound by:
What is the effector enzyme in the phosphoinositide signal transduction system?
All of the following are functions served by phosphatidylinositol bisphosphate EXCEPT: