PATHWAYS OF RAS FUNCTION - CONNECTIONS TO THE ACTIN CYTOSKELETON

Ras plays a central role in the cellular responses to many factors—namely, guanine nucleotide exchange factors (GEFs), guanine nucleotide dissociation stimulators (GDIs), and Guanine triphosphatase (GTPase)-activating proteins (GAPS). The recent advances in the biological and biochemical mechanisms of signal transduction involving Ras proteins are also reviewed in the chapter. The evidence connecting Ras to two intracellular signal transduction pathways that control transcription and cytoskeletal actin organization is also summarized in the chapter. Model for signal transduction in upstream and downstream pathways of Ras—mitogen-activated protein kinase (MAPK) pathway and Rho/Rac pathway—is presented in the chapter. MAPK pathway includes a set of cytoplasmic growth factor-regulated serine/threonine kinases that act on both ribosomal and nuclear factors, whereas the Rho/Rac pathway includes a set of Ras-related GTP-binding proteins that control the spatial pattern of polymerized actin in the cell. The model hypothesizes the sequential formation of multiprotein complexes at or near the plasma membrane, whose signaling capabilities lead to changes in nuclear processes and cytoskeletal actin organization. The nomenclatures of Ras signal transduction pathway molecules are also tabulated in the chapter. Perspectives on Ras function from studies on the phenotypic reversion of Ras-transformed cells are also considered in the chapter. © 1993, Academic Press Inc.