Kinasekaskader

Kinasekaskader, or kinase cascade, refers to a sequential series of protein phosphorylation events that transmit and amplify signals within a cell. In these cascades, an initial signal activates a first kinase, which then activates a second kinase, and so on, often ending in changes to gene expression, metabolism, or cytoskeletal organization. Activation typically occurs by phosphorylation of specific residues in the kinase’s activation loop, enabling enzymatic activity and substrate phosphorylation.

A classic example is the mitogen-activated protein kinase (MAPK) cascade, which commonly follows a three-tier organization: a MAP kinase kinase kinase (MAPKKK) activates a MAP kinase kinase (MAPKK), which in turn activates a MAP kinase (MAPK). In humans, RAF acts as MAPKKK, MEK as MAPKK, and ERK as MAPK. Other MAPK cascades include JNK and p38 pathways, which respond to stress and inflammatory signals. While MAPK cascades are among the best characterized, numerous other kinase cascades exist, including various PI3K/AKT-related routes that propagate signals through sequential phosphorylation.

Regulation of kinase cascades involves multiple layers: scaffold proteins can organize kinases into signaling modules, phosphatases remove phosphates to terminate signals, and feedback loops shape duration and intensity. Spatial localization within the cell and the duration of signaling (transient versus sustained) also influence the outcome.

Kinase cascades play essential roles in development, cell proliferation, differentiation, and stress responses. Dysregulation is associated with diseases such as cancer and developmental disorders, making components of cascades frequent targets for therapeutic intervention, including inhibitors of RAF, MEK, and ERK.