Protein kinase A Totally Explained

Everything about Protein Kinase A totally explained

In cell biology, protein kinase A, refers to a family of enzymes whose activity is dependent on the level of cyclic AMP (cAMP) in the cell. PKA is also known as cAMP-dependent protein kinase ). Protein kinase A has several functions in the cell, including regulation of glycogen, sugar, and lipid metabolism.

Mechanism

Activation

Each PKA is a holoenzyme that consists of two regulatory and two catalytic subunits. Under low levels of cAMP, the holoenzyme remains intact and is catalytically inactive. When the concentration of cAMP rises (for example activation of adenylate cyclases by G protein-coupled receptors coupled to G_s, inhibition of phosphodiesterases which degrade cAMP), cAMP binds to the two binding sites on the regulatory subunits, which then undergo a conformational change that releases the catalytic subunits.

Catalysis

The free catalytic subunits can then catalyse the transfer of ATP terminal phosphates to protein substrates at serine, or threonine residues. This phosphorylation usually results in a change in activity of the substrate. Since PKAs are present in a variety of cells and act on different substrates, PKA and cAMP regulation are involved in many different pathways.
The mechanisms of further effects may be divided into direct protein phosphorylation and protein synthesis:

In direct protein phosphorylation PKA directly either increases or decreases the activity of a protein.
In protein synthesis PKA first directly activates CREB, which binds the cAMP response element, altering the transcription and therefore the synthesis of the protein. This mechanism generally takes longer time (hours to days).

Inactivation

PKA is thus controlled by cAMP. Also, the catalytic subunit itself can be regulated by phosphorylation.
Downregulation of protein kinase A occurs by a feedback mechanism: one of the substrates that's activated by the kinase is a phosphodiesterase, which quickly converts cAMP to AMP, thus reducing the amount of cAMP that can activate protein kinase A.

Anchorage

The 2 regulatory subunits of protein kinase A is important for localizing the kinase inside the cell, with the aid of A-kinase anchoring protein (AKAP), AKAP binds both to the regulatory subunits and to either a component of cytoskeleton structure or a membrane of an organelle, anchoring the enzyme complex to a particular subcellular compartment.
The catalytic function of protein kinase A would sometimes couple with the AKAP, binding PKA together with phosphodiesterase to form a complex that functions as a signal module. For example, an AKAP locating near the nucleus of a heart muscle cell, would bind to both PKA and phosphodiesterase that hydrolyzes cAMP. As phosphodiesterase contributes to the steady low concentration of cAMP in unstimulated cells, as the cell is stimulated, PKA is then responsible for the activation of phosphodiesterase (adjacent to PKA) in order to lower the concentration of cAMP, in this condition, as PKA and phosphodiesterase has formed a complex, the proximity increase the efficiency of PKA's activity.

Function

PKA phosphorylates other proteins, altering their function. However, what proteins are available for phosphorylation depends on in what kind of cell the PKA activity is present, since protein composition varies from cell type to cell type. Thus, the effects of PKA varies with cell type:

Overview table

Further Information

Get more info on 'Protein Kinase A'.

External Link Exchanges

Do you know how hard it is to get a link from a large encyclopaedia? Well we're different and will prove it. To get a link from us just add the following HTML to your site on a relevant page:

<a href="http://protein_kinase_a.totallyexplained.com">Protein kinase A Totally Explained</a>

Then simply click through this link from your web page. Our crawlers will verify your link, extract the title of your web page and instantly add a link back to it. If you like you can remove the words Totally Explained and embed the link in article text.
As long as your link remains in place, we'll keep our link to you right here. Please play fair - our crawlers are watching. Your site must be closely related to this one's topic. Any kind of spamming, dubious practises or removing the link will result in your link from us being dropped and, potentially, your whole site being banned.