The invention discloses nearly 300 novel phosphorylation sites identified in signal transduction proteins and pathways underlying human ATM/ATR kinase signaling pathways, and provides phosphorylation-site specific antibodies and heavy-isotope labeled peptides (AQUA peptides) for the selective detection, profiling and quantification of these phosphorylated sites/proteins, as well as methods of using the reagents for such purpose. Among the phosphorylation sites identified are sites occurring in the following protein types: DNA repair proteins, Adaptor/Scaffold proteins, Cell cycle regulation proteins, G Protein/GTPase Activating/Guanine Nucleotide Exchange Factor proteins, DNA binding proteins, DNA replication proteins, Kinases, Disease associated proteins proteins, Methyltransferase, Ubiquitin conjugating proteins, Proteases, Phosphatases, and Transcription proteins.