KinaseSubstratBeziehungen

Kinase substrate, sometimes stylized as KinaseSubstrat in shorthand, refers to a molecule that is modified by a kinase through phosphorylation. Kinases are enzymes that transfer a phosphate group from ATP to specific amino acids—typically serine, threonine, or tyrosine—on target substrates. Phosphorylation alters the substrate’s activity, interactions, localization, stability, or function, enabling dynamic control of cellular signaling.

Substrates can be proteins, peptides, or, in some contexts, other molecules. In cellular signaling, most substrates are proteins whose phosphorylation creates docking sites for downstream effectors or modulates enzymatic activity. The outcome of phosphorylation depends on the substrate and context, and can propagate or dampen signaling cascades.

Specificity and recognition are governed by multiple factors. Kinases recognize substrates through consensus motifs, local structural context, and docking interactions with regulatory domains or scaffold proteins. Substrate phosphorylation is often transient and context-dependent, varying with cell type, state, and subcellular localization. Identification of substrates relies on in vitro kinase assays, phosphoproteomics, and substrate-trapping or kinase-substrate capture techniques.

Regulation of kinase–substrate interactions involves temporal and spatial control, as well as opposing phosphatases that remove phosphate groups. Scaffold proteins and subcellular compartmentalization help ensure substrates are phosphorylated at the right time and place. Dysregulation of substrate phosphorylation is linked to diseases such as cancer, metabolic disorders, and neurodegeneration.

Clinically, kinases are major drug targets, with therapies aimed at inhibiting catalytic activity or substrate access. Well-characterized relationships include ERK kinases phosphorylating transcription factors like ELK1, AKT phosphorylating GSK3 to inhibit it, and CDKs phosphorylating retinoblastoma protein to drive cell-cycle progression.