Kinases

Kinases (from grch. kinein - move) are enzymes (transferases - EC 2) that transfer a phosphate residue from a nucleoside triphosphate (e.g. ATP) to target molecules and thus phosphorylate them (phosphotransferases). Along with aminotransferases and glycosyltransferases they belong to the class of transferases.

The kinases are classified according to their phosphorylation site on the substrate. For example, the receptor tyrosine kinases, the serine threonine kinases and the cytoplasmic tyrosine kinases. These kinases play a crucial role in intra- and intercellular signal transduction and are often proto-oncogenes.

Besides the receptor kinases and the receptor-associated kinases, there are numerous cytoplasmic kinases. They are activated by second messenger, activated G proteins or by "upstream" kinases. Cytoplasmic (cytosolic) kinases are responsible for the phosphorylation of metabolic enzymes, cytoskeleton proteins and transcription factors.

Kinases in sugar metabolism: A group of kinases phosphorylates hydroxyl groups of sugar molecules. These are found in both phases of glycolysis, among others. For example, glucose is phosphorylated to glucose-6-phosphate. This step is catalyzed by the kinase "hexokinase". In a later step, the resulting sugar is catalyzed by another kinase, phosphofructokinase to fructose-1,6-bisphosphate. This sugar now carries a phosphate group at both ends. The fine interplay of substrate phosphorylation and dephosphorylation by inositol phosphate kinases and phosphatases is also of great importance for other sugars, e.g. for inositol.

Protein kinases: Protein kinases represent a distinct family of kinases. They form the second most abundant protein class in higher cells. Protein kinases are enzymes that capture alcoholic amino acid residues of proteins as substrate. Protein kinases (7 main groups with > 500 human protein kinases are known), form the second most abundant protein class in higher cells.

Among the protein kinases (protein kinase A, B, C) there are multifunctional enzymes that phosphorylate numerous protein substrates and highly specific protein kinases that can phosphorylate only a single protein.

The action of these kinases can be reversed by specialized protein phosphatases (hydrolases). Protein kinases (as well as their counterparts the protein phosphatases) are important regulators of cellular functions. Thus, they are significantly involved in signal transduction and the coordination of complex functions such as the cell cycle.

Other biologically relevant kinases:

Myosin light chain kinase (MLKK): Myosin light chain kinase, or MLKK, is an enzyme in the class of kinases that is detectable in myosin. This type of kinase plays an important role in smooth muscle contraction. The task of MLKK is to phosphorylate the myosin light chain, which in its unphosphorylated form prevents smooth muscle contraction.

Raf kinases: Raf kinases (abbreviation for rapidly accelerated fibrosarcoma or rat fibrosarcoma) also play an important role in the MAP kinase signaling pathway. RAF kinases play a key role in tumorigenesis. Regulation is likely through the small G protein Ras (acronym for "rat sarcoma"), which must be present in its active, GTP-bound form.

Creatine kinase (CK): Creatine kinase, also known as creatine phosphokinase (CPK), plays an important role in energy production and provides energy to cells. Creatine kinases are found in all muscle cells and in the brain. The 4 variants of creatine kinase are found in different organs, e.g. creatine kinase-MB (CK-MB) in the heart muscle. Total CK is the sum of all creatine kinases in the body.

Multifunctional kinases: Multifunctional kinases phosphorylate metabolites as well as other proteins. For example, phosphoglycerate kinase 1 (PGK1) phosphorylates 3-phosphoglycerate to 1,3-diphosphoglycerate. Furthermore, phosphoglycerate kinase 1 phosphorylates other proteins such as Beclin 1 (involved in autophagy), PDHK1 (pyruvate metabolism), and Bcl2 (apoptosis).

Atypical kinases: Atypical kinases do not have a sequence similar to typical kinases. However, they are thought to have enzymatic activity, and some appear to have a structural fold similar to typical kinases. An example of an atypical kinase is a truncated isoform of protein kinase C. This probably arises from alternative splicing of exons of the coding gene and posttranslational processing.