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00925njm 22002777a 4500 dc Rojas-Cabañeros, Jose Maria author Oliva-Martinez, Jose Luis author Santos, Eugenio author 2011-03 The Son of Sevenless (Sos) factors were originally discovered 2 decades ago as specialized Ras activators in signaling pathways controlling the process of R7 cell development in the eye of Drosophila melanogaster. The 2 known members of the mammalian Sos family (Sos1 and Sos2) code for ubiquitously expressed, highly homologous (69% overall) proteins involved in coupling signals originated by cell surface receptor tyrosine kinases (RTKs) to downstream, Ras-dependent mitogenic signaling pathways. Mechanistically, the Sos proteins function as enzymatic factors interacting with Ras proteins in response to upstream stimuli to promote guanine nucleotide exchange (GDP/GTP) and subsequent formation of the active Ras-GTP complex. In this review, we summarize current knowledge on structural, regulatory, and functional aspects of the Sos family, focusing on specific aspects of Sos biology such as structure-function relationship, crosstalk with different signaling pathways, and in vivo functional significance as deduced from phenotypic characterization of Sos knockout mice and human genetic syndromes caused by germline hSos1 mutations. Genes Cancer. 2011;2(3):298-305 10.1177/1947601911408078 1947-6027 1947-6019 Genes & cancer https://pmc.ncbi.nlm.nih.gov/articles/PMC3128634/ 21779500 http://hdl.handle.net/20.500.12105/7002 RTK Ras Ras-GEF Sos signaling Mammalian son of sevenless Guanine nucleotide exchange factors: old concepts and new perspectives