kinasesubstrate

A kinase substrate, or kinase substrate, is a molecule that is phosphorylated by a protein kinase. Phosphorylation typically transfers a phosphate group from ATP to an amino acid residue such as serine, threonine, or tyrosine in a protein, or to a lipid or other substrate in non-protein targets. This modification modulates the substrate’s activity, interactions, localization, and stability, and serves as a central mechanism in cellular signaling.

Substrate recognition and specificity arise from multiple factors. Kinases display preference for particular amino acid motifs, docking interactions, and regulatory subunits that help position the substrate for catalysis. Some substrates fit defined consensus sequences, while others rely on three-dimensional structure or adaptor proteins that bring the kinase and substrate together. Substrate availability and subcellular localization also influence whether phosphorylation occurs.

Substrates are diverse. Many are proteins, including enzymes, transcription factors, receptors, and cytoskeletal components. Some kinases act on small molecules or lipids; lipid kinases modify membrane phospholipids to produce second messengers that propagate signaling cascades. In all cases, phosphorylation can alter the substrate’s enzymatic activity, interaction networks, cellular localization, or degradation rate.

Detection and study of kinase substrates employ in vitro kinase assays, mass spectrometry to identify phosphorylation sites, and phospho-specific antibodies, along with computational motif and structural analyses. Mapping substrate networks helps illuminate signaling pathways and regulatory circuits.

Dysregulation of kinase substrates is implicated in diseases such as cancer, metabolic disorders, and neurodegeneration, making substrate identification important for understanding biology and identifying therapeutic targets.