What is a kinase or protein kinase substrate
In general terms, a kinase substrate or protein kinase substrate is a molecule or molecular structure, such as a peptide, oligonucleotide or any other small molecule that can fit into the specific catalytic binding pocket of the kinase.
Based on the definition for a kinase or protein kinase basically any molecule or molecular structure that can fit and bind into the recognition site of the specific kinase is a protein kinase or kinase substrate. Any compound or molecule that contains a functional group that can accept the specific modification group, for example a phosphate group, or contains the specific structure that fits into the binding pocket of the kinase, can act as a protein kinase substrate or a substrate for a kinase. If this protein kinase substrate can fit into the catalytic binding pocket but does not accept the transferred functional group, e.g. the phosphoryl group, the substrate can block the catalytic binding pocket and act as an inhibitor thereby modifying the catalytic activity of the specific kinase or protein kinase.
Various kinases act on small molecules such as lipids, carbohydrates, amino acids, nucleotides, and others. For example, a polynucleotide kinase can be used to transfer a γ-phospho group from ATP to the 5’-end of a polynucleotide that has a free 5’-OH group. If this group is radioactive the reaction can be used to label the target molecule with a radioactive tracer. In general, since kinases are mostly known for the transfer of a phosphate group from a higher energetic molecule to their substrate the majority of kinases are involved in signaling pathways that involve the transfer of a phosphate group. This reaction is called phosphorylation. The addition and removal of phosphoryl groups provides the cell with a control mechanism that can respond to different conditions or signals.
Kinases are classified into broad groups based on the substrate they act upon. The list of kinases includes protein kinases, lipid kinases, and carbohydrate kinases.
According to Cheek et al. (2002), kinases are a ubiquitous group of enzymes that catalyze the phosphoryl transfer reaction from a phosphate donor, usually from an ATP molecule, to a receptor substrate. Basically, almost all kinases catalyze essentially the same phosphoryl transfer reaction but display a remarkable diversity in their substrate specificity, structure, and the signaling pathways in which they participate.
The specificity of protein kinases are primarily determined by the amino acids around the phosphorylation sites. This indicates that the amino acid sequence of the phosphorylation site contains a specific peptide sequence motif unique to an individual protein kinase. Protein kinases transfer the terminal ATP phosphate group to the serine, threonine, or tyrosine residues of substrate proteins. The phosphorylated forms of many enzymes are much more active than the unphosphorylated forms. In the human genome, the protein kinase family is one of the largest protein family involved in the regulation of multiple biological processes via posttranslational phosphorylation of serine, threonine, and tyrosine residues. The human genome contains 500 protein kinase genes that constitute about 2% of all genes. Approximately 2000 protein kinases are encoded by the human genome. Protein kinases together with protein phosphatases play important roles in the regulating of metabolism, cell growth, cell motility, cell differentiation and cell division, and are part of signaling pathways involved in normal development and disease.
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Web links for phosphorylation sequence motifs: