The role of SSeCKS/Gravin/AKAP12 scaffolding proteins in the spaciotemporal control of signaling pathways in oncogenesis and development

Scaffolding proteins are thought to facilitate the efficiency and specificity of enzyme/substrate reactions by coordinating their interaction along a cytoskeletal infrastructure in a spatial and temporal manner. Rodent SSeCKS, and its human orthologue. Gravin, seem to function as tumor suppressers and regulators of mitogenesis, inflammatory response, development and differentiation via novel scaffolding functions involving the selective binding of key Gl --> S phase signaling proteins such as protein kinase C (PKC), PKA, calmodulin, cyclins and beta-adrenergic receptors. The association of SSeCKS/Gravin with the actin-based cytoskeleton as well as to plasma membrane sites via N-terminal myristylation places these proteins at the junction of signaling and cytoskeletal pathways. The following review describes the regulatory and scaffolding functions of SSeCKS and Gravin and how mitogen-induced phosphorylation modulates their ability to regulate cell adhesion, signaling, mitogenesis and oncogenesis.