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 spacial and temporal manner. Rodent SSeCKS, and its human orthologue, Gravin, seem to function as tumor suppressors and regulators of mitogenesis, inflammatory response, development and differentiation via novel scaffolding functions involving the selective binding of key G1-->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.
Gelman
Irwin H
IH
Dept. of Medicine & Ruttenberg Cancer Center, Division of Infectious Diseases, Mount Sinai School of Medicine, New York, NY 10029-6574, USA. irwin.gelman@mssm.edu
D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000737:chemistry / Q000502:physiology; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry / Q000502:physiology; D003598:Cytoskeletal Proteins; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D008934:Mitogens / Q000737:chemistry / Q000502:physiology*; D008969:Molecular Sequence Data; D011506:Proteins / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013379:Substrate Specificity / Q000502:physiology
D054758:A Kinase Anchor Proteins; C491162:AKAP12 protein, human; C119719:AKAP9 protein, human; D048868:Adaptor Proteins, Signal Transducing; C102361:Akap12 protein, rat; C486537:Akap9 protein, rat; D001324:Autoantigens; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D008934:Mitogens; D011506:Proteins; D017868:Cyclic AMP-Dependent Protein Kinases