Protein Kinase A’s Regulation of Cell Proliferation

Protein Kinase A (PKA) is a specific enzyme within the cAMP pathway which not only is utilized for endocrine signaling cascades but also used for cell regulation in proliferation. One particular and basic method is listed below:

Binding of a particular ligand to a specific G protein coupled receptor (GPCR) causes the exchange of GDP for GTP on the alpha subunit of the G protein. This activation of the G protein causes the dissociation of the alpha subunit from the others. Such alpha subunit, still carrying an active GTP, attaches to an adenylyl cyclase, which activates the cyclase and causes the conversion of nearby ATP molecules to cAMP molecules. Such cAMP molecules act as a secondary messenger, which seeks out to bind to Protein Kinase A.

PKA is interesting in that it has two catalytic subunits and two regulatory subunits. Such interaction between the catalytic and regulatory subunits is called protein-protein interaction. However, PKA is also affected by allosteric regulation (binding of small molecules), which we shall see.

The cAMP created by adenylyl cyclase now attach themselves to the regulatory subunits of PKA. Once two separate cAMP bind with each of the regulatory subunits, the secondary messenger causes the activation and release of the catalytic subunits. These catalytic subunits can then enter the nucleus and affect transcription of DNA.

Catalytic subunits’ entrance into the nucleus causes them to seek out a transcription factor called CREB (cAMP response element binding protein), which is bound to a CRE (cAMP response element). Upon encountering a CREB, PKA catalytic subunits phosphorylates it. Such phosphorylation causes CREB to recruit a coactivator, which thus finally causes translation to occur. Such is important for many of the genes targeted by CREB are actually involved in regulating cell proliferation, survival and differentiation. Thus, by activation of PKA by cAMP, which itself is created by adenylyl cyclase, which itself is activated by a G protein, which first was activated by a ligand binding to a receptor, cell proliferation is allowed to occur!

As a side note, after the need is expended, the alpha subunit G protein’s GTP will be hydrolyzed back to GDP, thus inactivating it. The inactivation causes the different subunits to reform and reattach to its receptor.