Description: The article focuses on ampk activator. It is an overview of AKT signaling pathway containing the aspects of regulation and downstream effects. There will be a lesson on a ket signaling, introducing a ket signaling pathway and going over the downstream effects of a ket signaling pathway and how the pathway is regulated.
This lesson is on a ket signaling, so in this lesson, we’re going to introduce a ket signaling pathway and we’re going to look at the downstream effects of a ket signaling pathway as well as how the pathway is regulated.
What is a KT? A KT is also known as protein kinase B and it is a serine and threonine kinase, so it means that it leads to the phosphorylation of serine and threonine residues on target protein. there are three isoforms of a KT akt1 also known as protein kinase B alpha a KT, also known as protein kinase B beta and a KT 3 also known as protein kinase B gamma.
We’ll get into the specific details and the specific actions each of these ice forms has in another lesson, so this lesson will be primarily focusing on akt1 signaling, so a KT is regulated by growth signals and it is involved in various disease states including cancer, insulin resistance, type-2 diabetes, cardiovascular diseases and autoimmune diseases.
When we look into the signaling pathway, we’ll be able to understand why a cutie is associated with these types of diseases, so how does ADT signaling occur in the cell? It all begins at the cell membrane with the activation of either a receptor tyrosine kinase or a g-protein coupled receptor now.
These are two different types of receptors, but both lead to the activation of a KT, as I mentioned before, growth signals activate a KT signaling and one of the growth signals or growth factors is insulin, so I’ve talked about insulin signaling before in another lesson.
If you haven’t watched that lesson, I would suggest you watch that to better understand insulin signaling, when either of these receptors is activated, they lead to the recruitment of a pi3 kinase or a phosphatidyl inositol 3 kinase now pi3k leads to an increase in pip 3 levels or fossil inositol triphosphate which leads to the recruitment of PD k1 now PDK.
One can directly phosphor the akt at 300 308 to activate a Katy or it can activate mTOR complex to indirectly which itself can phosphorylate a Katie at serine 473 to activate a Katie, so these are two important phosphorylation sites on a Katie which lead to its activation.
So when a Katie is activated, what does a Katie do in the cell? One of the main things that a Katie does is that it inhibits as160 through phosphorylation now as160, as you may have learned in my insulin signaling video, it is a negative regulator of glute 4 translocation which means that when a cake inhibits as160 the cell is able to translocate glute for containing vesicles which leads to glute for being deposited in the membrane and allowing glucose to enter the cell and undergo glycolysis.
Another thing a key T does in the cell is that it inhibits tuberous sclerosis complex 1 & 2 through phosphorylation, so you may be thinking, what is T SC 1 & 2? T SC 1 & 2 is a negative regulator of mTOR complex one, so normally t SC 1 & 2 inhibits Reb or RH EB which is an activator of mTOR complex 1, so by a KT inhibiting t SC 1 & 2, it activates mTOR complex 1 which leads to the activation of P 1706 kinase and ribosomal s6 which leads to protein synthesis, so a KT activation leads to increase in protein synthesis.
Another thing in poor complex 1 does is that it inhibits otology and it inhibits autopsy by several mechanisms and if you want more information on those mechanisms, I suggest you check out my macro toppity video and my mTOR signaling videos, so a KT activates mTOR complex 1 it up regulates protein synthesis and down regulates etapa G.
Another major protein that a KT regulates is FOXO and it inhibits FOXO through phosphorylation now foxhole inhibits cell survival and proliferation which means that a KT increases cell survival and proliferation.
Another protein that a KT inhibits through phosphorylation is GSK 3 or glycogen synthase kinase 3 glycogen synthase kinase 3 as its name suggests, phosphorylates glycogen synthase to inactivate glycogen synthase through phosphorylation glycogen synthase, as we’ve learned before, is critical or needed for glycogen synthesis, so this means that because a KT inhibits an inhibitor of glycogen synthesis, it activates glycogen synthesis.
So a KT activates glycogen synthesis and finally a KT activates ATP citrate lyase and ATP citrate lyase is important for fatty acid synthesis, so a KT activates fatty acid synthesis as well through ATP citrate lyase because of many functions of a KT signaling pathway, we now can understand why a KT is so important in diseases such as insulin resistance and diabetes as well as cancer.
When the a KT signaling pathway is completed, how does this pathway shut off? There are a couple of ways that the Akt pathway can turn off and one of those ways is at the beginning of the pathway p10 which is a phosphatase down regulates pip 3 and it does so by converting pip 3 into pip 2.
So this can shut off this step so that PD K 1 is not recruited and activated, another way that a KT signaling is turned off which is through another phosphatase pH L PP and this phosphatase D phosphorylates a Katie at serine 473, so this is another way that the cell can turn off a kt signal.
Finally, the last phosphatase that can turn off a KT signaling is protein phosphatase 2a or PB 2a which D phosphorylates a Katie at threonine 308, so these are a few ways the akt signaling pathway can be turned off.
We’ve seen the a KT signaling pathway, we can summarize what the pathway performs and one of the things that it does is that it increases glucose uptake in utilization. As we’ve mentioned before, it leads to the inhibition of as160 which leads to glute 4 translocation and glucose uptake and utilization in glycolysis, it also leads to glycogen synthesis, because it leads to the activation of glycogen synthase, so that means that the cell can uptake glucose more readily and also store the glucose as glycogen for later use ad D signaling also increases fatty acid synthesis through ATP citrate lyase activation.
It also increases protein synthesis through mTOR complex one activation and then finally a KT signaling leads to increases in cell survival and proliferation through negative regulation on FOXO proteins.
As you can see, a KT signaling leads to the synthesis of macromolecules and leads to cell survival in polarization and finally a KT signaling leads to the inactivation or suppression of a toff eg through mTOR complex one signaling.
So if we could describe a KT signaling in one statement, what could we say? A KT signaling does well, a kicky signaling increases in AB ilysm and decreases catabolism, so we can see that it increases in AB ilysm through the synthesis of macromolecules in glycogen fatty acids and proteins and it also decreases catabolism by decreasing functions in processes such as etaf eg, I hope you found this video helpful, if you did, please like and subscribe for more videos like this one, thank you so much and I’ll see you next time.