Increasing complexity of Ras signaling

摘要: The initial discovery that ras genes endowed retroviruses with potent carcinogenic properties and the subsequent determination mutated were present in a wide variety of human cancers, prompted strong suspicion growth-promoting actions Ras proteins contribute to their aberrant regulation growth stimulatory signaling pathways. In 1993, remarkable convergence experimental observations from genetic analyses Drosophila, S. cerevisiae C. elegans as well biochemical biological studies mammalian cells came together define clear role for signal transduction. What emerged was an elegant linear pathway where functions relay switch is positioned downstream cell surface receptor tyrosine kinases upstream cytoplasmic cascade included mitogen-activated protein (MAPKs). Activated MAPKs turn regulated activities nuclear transcription factors. Thus, every component between nucleus defined conserved worms, flies man. This achievement our efforts appreciate how function may malignant cancer cell. However, identification this has proven be just beginning, rather than culmination, understanding Instead, we now simple represents but minor very complex circuitry. involve array pathways, cross-talk, feedback loops, branch points multi-component complexes are recurring themes. simplest concept cascade, each simply relays same message next, clearly not case. review, summarize current transduction emphasis on new complexities associated recognition and/or activation cellular effectors, diverse pathways mediated by interaction Ras-subfamily multiple effectors.