Elucidation of cellular signaling networks requires methodologies for large-scale quantitative phosphoproteomic analysis that can reveal dynamic system-wide changes in protein phosphorylation. Recent technological advances in mass spectrometry-based proteomics have enabled us to make a large-scale identification of signaling molecules through the enrichment of phosphorylated proteins or peptides [12, 13] . One of the most widely used and well known strategies currently used in phosphoproteomic studies is stable-isotope labelling by amino acids in cell culture (SILAC). Although introduced relatively recently, SILAC has been used extensively in the proteomics community [14] . With SILAC, the entire proteome of a given cell population is metabolically labeled by heavy, non-radioactive isotopic variants of amino acids, thus making it distinguishable by MS analysis [15, 16] . Thereafter, two or more distinctly SILAC-labeled cell populations can be mixed and analyzed in one MS experiment, allowing accurate quantization of proteins from the different cellular states. By coupling with a phosphoprotein or phosphopeptide enrichment method, such as titanium dioxide (TiO 2 ) [17] , strong cation exchange (SCX) [18] , or the two in combination [19] , SILAC has been widely applied to profile dynamic phosphorylation changes in signal transduction [20, 21] .