Insulin action on the skeleton is essential for bone development, remodeling and whole-body energy metabolism but a global view of the signal transduction in this tissue is lacking. Furthermore, whether there are signaling differences in bone that drive transcriptional rewiring and proteome remodeling under insulin resistant or ageing conditions is also incompletely understood. Therefore, we performed a phosphoproteomic and proteomic analysis of insulin signaling in the bones of young lean insulin sensitive verses old obese insulin resistant mice revealing a marked rewiring of phosphorylation. We targeted dysregulated phosphoproteins in a zebrafish functional genomic screen of bone growth, development and mineralization revealing novel candidates important for skeletal formation. One of these was ALF Transcription Elongation Factor 4 (AFF4), the core scaffold of the Super Elongation Complex (SEC) and we show that phosphorylation of S831 on AFF4 is a novel insulin-dependent substrate of P70S6K. Phosphorylation of S831 is defective in insulin resistant osteoblasts and associated with reduced transcriptional elongation at discrete locations in the genome. Mechanistically, we show that phosphorylation of S831 on AFF4 regulates insulin-dependent recruitment of AF9/ENL into the SEC and promotes gene-specific activation. Taken together, our integrated phosphoproteomic/proteomic and functional genomic analysis has identified novel regulators of insulin action on the skeleton, further uncovering a new mechanism of insulin resistance via defective insulin-stimulated transcriptional elongation and gene activation.