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Increasing Complexity of Ras Signal Transduction: Involvement of Rho Family Proteins

1997; Elsevier BV; Linguagem: Inglês

10.1016/s0065-230x(08)60700-9

2162-5557

Roya Khosravi‐Far, Sharon L. Campbell, Kent L. Rossman, Channing J. Der,

Melanoma and MAPK Pathways

The chapter illustrates current understanding of Ras signal transduction, with emphasis on the involvement of Rho family proteins and on how Rho family proteins contribute to Ras function. A remarkable convergence of experimental observations from genetic analyses of Drosophila melanogaster, Saccharomyces cerevisiae, and Caenorhabditis eleguns, as well as biochemical and biological studies in mammalian cells, together define a clear role for Ras in signal transduction. This remarkable achievement appreciates how the aberrant function of Ras proteins contribute to the malignant growth properties of the cancer cell. Ras signaling involves a complex array of signaling pathways, in which cross-talk, feedback loops, branch points, and multicomponent signaling complexes are recurring themes. The chapter summarizes two major emerging themes that refocus the perceptions of how Ras functions in signal transduction. First, it has become clear that the Raf-1 serine/threonine kinase is not the sole downstream effector of Ras. Second, the functions of certain Ras-related proteins that constitute part of the Rho family proteins are shown to be important for Ras transformation. This, together with evidence implicating these small guanosine triphosphates (GTPases) downstream of Ras, has prompted considerable effort in understanding how the function of Rho family proteins contribute to Ras signaling and transformation.