ScaffoldProteine

Scaffoldproteine, or scaffold proteins, are non-enzymatic proteins that organize components of signaling pathways into multiprotein complexes. By assembling receptors, kinases, phosphatases, and adaptors in close proximity, they increase local substrate concentrations, enhance signaling efficiency, and improve specificity while reducing unwanted cross-talk. Scaffold proteins often influence the dynamics of signaling, shaping response time, duration, and amplification.

Structurally, scaffold proteins are typically modular and may contain interaction domains such as SH3, PDZ, LIM, or PH motifs, coiled-coil regions, or intrinsically disordered segments. This modularity allows them to bind multiple partners and to localize signaling modules to particular cellular compartments, such as the plasma membrane, cytosol, or organelles. Regulation occurs through post-translational modifications, changes in expression, subcellular localization, and interaction with other regulators, enabling dynamic assembly and disassembly of signaling complexes.

Scaffold proteins are found across many pathways, including MAPK, Wnt, and cAMP signaling. Examples include Ste5 in yeast, which assembles the pheromone-response MAPK cascade by binding the kinases Ste11, Ste7, and Fus3; Axin, which scaffolds the β-catenin destruction complex in the Wnt pathway; and AKAPs, which anchor PKA and other enzymes at specific subcellular sites. Kinase suppressors of Ras (KSR1/2) act as scaffolds for the Raf–MEK–ERK cascade in mammalian cells.

Aberrant scaffold function can contribute to disease by disrupting signaling specificity or timing. Because scaffold proteins coordinate multiple interactions, they are of interest as potential targets to modulate signaling pathways with reduced off-target effects.