Actions of the Second Messenger and Protein Kinase A

by Kevin Ahern, PhD

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    00:02 So the cyclic AMP as a second messenger has to interact with other molecules to cause that signal to be transmitted because if it doesn’t, then there won’t be a signal.

    00:10 Well it turns out that cyclic AMP goes and interacts with a protein known as protein kinase A.

    00:17 Now protein kinase A as its name suggests is a protein of course, and it’s also an enzyme.

    00:23 But in the normal state, protein kinase A is in the inactive form, meaning it’s not catalyzing any reaction.

    00:30 And that’s because the protein kinase A has its catalytic part of itself having been covered up.

    00:38 The covering up of the catalytic part prevents the catalytic part from catalyzing a reaction.

    00:44 So we can see that in this depiction here.

    00:46 We see that protein kinase A has four subunits associated with it.

    00:50 Two units that are in red with an R in them, indicating that they’re regulatory subunits.

    00:54 And these subunits are covering up that catalytic site.

    00:58 The two C subunits in blue are where the catalytic site is located.

    01:03 Well here comes our four molecules of cyclic AMP that has been produced by the adenylate cyclase in the previous reaction. What happens is, these four cyclic AMPs convert the inactive form of protein kinase A into the active form. And the way they do that is by binding to the regulatory subunits. Now as we’ve seen time and again in these lectures, binding of a molecule to a protein, slightly changes that protein’s shape, in this case the regulatory subunits. And the regulatory subunits with their change in shape can no longer bind to the catalytic subunits.

    01:38 Consequently the catalytic subunits are released and now their catalytic sites are open and exposed to all the molecules in the cell.

    01:47 They can begin to catalyse reactions.

    01:49 So now we see the information from the hormone outside the cell has been communicated all the way to protein kinase A.

    01:57 And we still have a ways to go.

    02:00 What protein kinase A’s catalytic subunits do, is they catalyze the addition of phosphates to the side chains of serine and threonine amino acids within a protein.

    02:12 This is the covalent modification that I talked about before.

    02:15 So we can see this modification happening starting with an unphosphorylated or unmodified protein on the left and the modified protein on the right.

    02:25 The phosphate that’s put onto the side chains of the serines and threonines comes there from a molecule of ATP, which transfers onto serine’s and threonine’s side chains in a process that we call phosphorylation.

    02:41 Now protein kinase A phosphorylates many proteins.

    02:45 And phosphorylating those proteins causes their activities to change.

    02:50 Protein kinase A for example, phosphorylates proteins in glycogen metabolism.

    02:55 Two of the proteins that it phosphorylates are known as glycogen synthase, which catalyzes the formation of glycogen.

    03:02 And another protein known as phosphorylase kinase or PK, that activates glycogen breakdown.

    03:11 The cell’s decision to either make glycogen or break down glycogen comes as a result of action of this hormone system that I’ve described here.

    03:22 Let’s watch to see what happens in this process.

    03:25 Here’s the catalytic subunit of protein kinase A that was released in the process of the previous slide.

    03:30 We can see glycogen synthase labeled in S, and we see that it gains a phosphate.

    03:36 Now in this scheme I’m showing you here, the enzymes that are active are shown in green, and the enzymes that are inactive are shown in red.

    03:44 So we see in this case that glycogen synthase started out in the active form but it got a phosphate put onto it and that converted it into the inactive form.

    03:53 But protein kinase A also works on phosphorylase kinase as I said.

    03:58 And phosphorylase kinase, when it gains a phosphate, it’s converted from the inactive form in red to the active form in green. What phosphorylase kinase will do is go further and activate the breakdown of glycogen. So the action of this hormone signaling system is to turn off the synthesis of glycogen and to turn on the breakdown of glycogen at the same time. What active phosphorylase kinase does is convert an enzyme known as glycogen phosphorylase from the inactive form to the active form by adding a phosphate to it. So phosphorylase kinase is a protein that can add a phosphate to another protein. What glycogen phosphorylase a does, the active form, is it breaks down glycogen. And what glycogen synthase does when it’s active is make glycogen. So this process that I’ve described to you here, as I said earlier is simultaneously turning off the glycogen synthesis at the same time as it’s turning on glycogen breakdown. That process as I've described in a previous lecture is known as reciprocal regulation. The same process having opposite effects on catalytic-- catabolic and anabolic pathways.

    About the Lecture

    The lecture Actions of the Second Messenger and Protein Kinase A by Kevin Ahern, PhD is from the course Hormones and Signal Transduction. It contains the following chapters:

    • Actions of the Second Messenger
    • Protein Kinase A

    Included Quiz Questions

    1. Glycogen synthase catalyzes glycogen formation.
    2. Phosphorylation activates all of the enzymes.
    3. Phosphorylation inactivates all of the enzymes.
    4. Glycogen synthesis and breakdown occur simultaneously.
    1. The binding of epinephrine stops glycogen synthesis.
    2. When glycogen synthase is phosphorylated, it is active.
    3. When glycogen synthase is phosphorylated, it is inactive.
    4. The production of cAMP activates protein kinase A.
    5. The binding of epinephrine stimulates glycogen synthesis.
    1. Prevent the concurrent activity of 2 closely parallel metabolic pathways.
    2. Facilitate the concurrent activity of 2 closely parallel metabolic pathways.
    3. Prevent the concurrent inhibition of 2 separate metabolic pathways.
    4. Prevent the concurrent activity of 2 entirely unrelated metabolic pathways.
    5. Facilitate the concurrent activity of 2 entirely unrelated synthesis pathways.
    1. The phosphorylation of phosphorylase kinase enzyme by PKA leads to activation of glycogen breakdown.
    2. PKA is a structural protein essential for the maintenance of cell membrane morphology.
    3. The activated PKA enzyme inhibits glycogen synthesis by inactivating the glycogen synthase enzyme via the phosphorylation process.
    4. The activated PKA enzyme plays a crucial role in the reciprocal regulation of glycogen metabolism.
    5. Protein kinase A enzyme is composed of 4 subunits (2 regulatory and 2 catalytic).

    Author of lecture Actions of the Second Messenger and Protein Kinase A

     Kevin Ahern, PhD

    Kevin Ahern, PhD

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