Updated project metadata. The innate immune response relies on efficient, robust and fast protein signaling networks to relay information related to pathogen or viral detection. This communication is mediated primarily through protein-protein interactions and post-translational modifications (PTMs), events which are best characterized by mass spectrometry (MS)-based proteomics. This in-depth study uses MS to identify changes in protein signaling networks of Lipopolysaccharide (LPS)-stimulated human and mouse macrophages, at the level of single PTMs (via phosphorylation and ADP-ribosylation site ID) and protein complexes (via size exclusion chromatography and immunoprecipitation). The result is a curated meta-database of 6,475 proteins including 2,311 ADP-ribosylated proteins and 2,284 phosphoproteins present in LPS-stimulated macrophages. Follow up studies characterized the ASK protein complex – which appeared to dissociate upon LPS stimulation – and a complex which formed upon LPS stimulation and contained the poly(ADP-ribosyl) transferase PARP9 protein.