What are Kinases ?? What are There Types ??
Kinases are a group of enzymes that
chemically incorporate substrate proteins with phosphate groups. These enzymes
are conserved during evolution. They are found in 3 domains of life. It is
interesting to note that nematodes, insects and vertebrates share some kinases
in common. As a family, kinases constitute 2% of the human genome and are
the third most populous protein groups. There are over 518 kinases encoded by
the human genome including both protein and lipid kinases and it has been
estimated that kinases regulate approximately 50% of the cellular functions and
because of these kinases have become the targets of interest in the treatment
of various types of diseases. Approximately 10% among these kinases are
pseudokinases as they lack the main residues required for the catalytic
activity. They all have a binding site for substrate protein, Mg2+-
ATP (Phosphate donor) and various regulatory sites. The process of
phosphorylation is temporary as the proteins phosphorylated get
dephosphorylated to the previous form of protein. Phosphorylation may bring
conformational changes, affect enzymatic activity, stability or degradation,
association with other proteins and localization within the cell. Kinases are
involved in various cellular functions like metabolism, regulation of cell
cycle, cell adhesion, migration, cellular differentiation and survival.
All protein kinases have N-terminal lobe
and C-terminal lobe that forms a cleft that serves as a docking site for ATP
beneath a glycine rich loop. Active and inactive forms of protein kinases
differ in structure. In the active state with the C-helix of the N-terminal
lobe bound to the β-core sheet, the N-lobe moves as a rigid body that opens and
closes as a part of the catalytic cycle.
The physiological role that a kinase will
play is determined by its effect on the substrate in response to a biological
stimulus. Specificity of a substrate is determined at both macromolecular and
micromolecular levels. Macromolecular level involves the specificity between
the kinase and the substrate protein. Micromolecular specificity is the ability
of the given kinase domain to recognize and phosphorylate a specific amino acid
within a substrate.
Dysregulation of these protein kinases is
implicated in various processes of carcinogenesis. Inhibiting these kinases has
led to the paradigm shift in cancer therapy. Almost half of the kinases are
mapped to known disease loci, cancer amplicons, mutations or their deregulation
can directly be related to human diseases.
Types of Kinases
Tyrosine kinases
are a large class of kinases that are membrane bound and phosphorylate tyrosine
residues using ATP which have a significant role in various signaling cascades
like proliferation, cell cycle, DNA damage response and inflammatory responses.
Tyrosine kinases include enzymes such as vascular
endothelial growth factor receptor (VEGFR), platelet-derived
growth factor receptor (PDGFR),
epidermal growth factor receptor (EGFR), stem
cell factor receptor and colony-stimulating
factor-1 receptor.
Serine/threonine kinases
are a group of kinases that phosphorylate the OH group of serine/threonine.
They are a family of kinases which are of drug targeting interest in areas
other than oncology. There are 2 classes of these kinases: Protein kinase C
(PKC) and cyclin dependent kinase (Cdk). PKC is a class of enzymes where the
disruption of its activity leads to aging.
Lipid kinases
are those kinases which phosphorylate the lipids in the cells both on the
plasma membrane as well as membranes of the organelles. Lipid kinases are
therapeutic targets for chronic pain. Examples of lipid kinases are
Phospholipase C, PI3-kinases, PI4 kinases and Phosphatidylinositol phosphate
kinases.
Pseudokinases are
those kinases that have lost their catalytic ability due to the mutations in
the critical amino acids of the kinase domain. 48 out of 518 are pseudokinases.
They have important catalysis independent functions like scaffolding proteins.
These are also called inactive kinases.
Overall, it is found that the kinases are
key players in almost every cellular process acting as molecular switches
within complex networks of signals. Their functions are determined by the
nature of the phosphoryl group, the structure of the individual kinase and also
by many dynamic factors that regulate activity. With the continued discovery of
new substrates and mechanisms, there is no shortage of research remaining to be
pursued to further elucidate their physiological roles and their importance to
disease progression.
We, Biotechno Labs offer a wide range of kinase-related products including types of protein kinases, lipid kinases, assay kits, inhibitors of kinases, recombinant cell lines, receptors, substrates, GST tagged kinase products, biotinylated tagged kinase products, protein-protein interaction products.