{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSOS1 is a pivotal Ras‐specific guanine nucleotide exchange factor that couples activated receptor tyrosine kinases to Ras, initiating the Ras–MAPK signaling cascade by catalyzing the exchange of GDP for GTP on Ras. Its activity is tightly regulated by an autoinhibitory mechanism—mediated by distinct domains, including the DH, PH, and histone regions—that control access to an allosteric Ras‐binding site. Lipid signals such as phosphatidic acid promote SOS1 recruitment to cell membranes, thereby facilitating its activation, while interactions with adaptor proteins like GRB2 help cluster signaling complexes to ensure efficient downstream signal propagation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGain‐of‐function mutations in SOS1 have been implicated in several developmental disorders. In Noonan syndrome, for example, missense mutations in SOS1 disrupt regions critical for maintaining its autoinhibited conformation, resulting in enhanced Ras and ERK activation and contributing to a distinctive clinical phenotype. Similarly, truncating mutations in SOS1 have been linked to hereditary gingival fibromatosis, underscoring the importance of its carboxy‐terminal proline‐rich motifs for proper signal transduction. Moreover, genetic association studies even implicate SOS1 in metabolic conditions such as type 2 diabetes, highlighting its broad relevance for human disease."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jon C D Houtman, Hiroshi Yamaguchi, Mira Barda-Saad, et al. 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