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 kinasesare 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, BTL Biotechno Labs Pvt Ltd offer a wide range of kinase-related products from two eminent principals BPS biosciences and Carna Biosciences and the product range includes 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