# Structural Biochemistry/Kinase

There are specific enzymes that help perform function for a cell. A kinase is an enzyme that adds phosphate groups to proteins. This process is called phosphorylation. The importance of a kinase is that it marks the protein, instructing a cell to do something, such as to grow or to divide.

### Structure

A protein kinase has two lobes that are different in structure and functionality. These differences add to catalysis and regulation in different ways. These differences are also what make protein kinases different from other metabolic kinases, such as ATPases. The smaller one of these two lobes is called the N-lobe. This contains a beta sheet but is mostly helices. The helical part is the core of the structure and is the part that protein substrates attach to. The smaller lobe is called the N-lobe. This lobe consists of five stranded beta sheets, along with a helix.

### Evolution

Eukaryotic protein kinases (EPKs) divergently evolved from eukaryotic-like kinases (ELKs), which are structurally much simpler. Although ELKs also have the same two lobes along with the adenine ring, the C-lobe of the EPK have two extra parts. One is called the Activation Segment and the other is an extra helical subpart that allows substrates to attach. These new sites of the C-lobe allow EPKs to precisely function and be highly regulated. EPKs were evolved from ELKs to further achieve faster and more efficient regulation. Firstly, the Activation Segment was inserted. Later, the extra helix was attached to the C-lobe, and this is the structure of protein kinase that we know.

### Protein Kinase A (PKA)

Protein kinase A is an enzyme that covalently attaches phosphate groups to proteins. It is also known as the cyclic AMP-dependent protein kinase. An extremely significant characteristic of protein kinase A is its ability to be regulated by the fluctuation of cyclic AMP levels within cells. Essentially, protein kinase A is responsible for all cellular responses due to the cyclic AMP second messenger. Cyclic AMP activates protein kinase A, which phosphorylates specific ion channel proteins in the postsynaptic membrane, causing them to open or close. Due to the amplifying effect of the signal transduction pathway, the binding of a neurotransmitter molecule to a metabotropic receptor can open or close many channels.

### Protein Kinase B (PKB)

Protein kinase B regulates various biological responses to insulin and growth factors. Akt is another way to classify Protein Kinase B. Protein Kinase B is a serine-threonine-specific protein kinase that contributes to multiple cellular processes such as glucose metabolism, apoptosis, and cell migration.

### Protein Kinase C (PKC)

Protein kinase C catalyzes the process of signals mediated by phospholipid hydrolysis. It is activated by the lipid second messenger, diacylglycerol. This lipid second messenger serves as the key initiation for most protein kinase C's. Protein kinase C isozymes consist of a single polypeptide chain that possesses an amino-terminal regulatory region and a carboxy terminal kinase region. The isozymes are categorized into various groups: conventional protein kinase Cs which are regulated by diacylglycerol, phosphatidylserine, and Ca^2+ in addition to novel protein kinase Cs which are regulated by diacylglycerol and phosphatidylserine. Activation of GPCR's, TKR's, and non-receptor tyrosine kinases can lead to protein kinase activation by stimulation of either phospholipase Cs to yield diacylglycerol, or phospholipase D to yield phosphatidic acid and diacylglycerol. Additionally, conventional protein kinase Cs are regulated by Ca^2+.

## Tyrosine Kinase

Tyrosine kinases function in multiple ways that involve processes, pathways, and specific actions that are key in the body. Specific receptor kinases function in transmembrane signaling whares tyrosine kinases within the cell function entirely different in the sense that they are part of signal transduction in the nucleus. The activity of tyrosine kinases in the nucleus involve cell-cycle control, such as differentiation in the different phases when the cell begins division, and also show properties in controlling certain transcription factors. Tyrosine kinase activity is also seen in mitogenesis or in other words the induction of mitosis in the cell. Specifically during this induction, tyrosine kinases phosphorylate proteins in the nucleus and in the cytosol. In addition, tyrosine kinase has been seen to be involved in cellular transformation due to the phosphorylation of a middle-T antigen on tyrosine, a change that is similar to cellular growth or in reproduction.

### References

* ↑ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084033/
* ↑ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084033/
* ↑ http://www.vivo.colostate.edu/hbooks/molecules/pka.html
* ↑ http://jcs.biologists.org/content/118/24/5675
* ↑ http://www.upch.edu.pe/facien/facien2011/fc/dbmbqf/pherrera/cursos/receptores/pkc-cocb97.pdf