Upon binding of an antigen to the IgM molecule the ITAM tyrosines become BF-170 hydrochloride phosphorylated by Src family kinases, an event resulting in recruitment of the spleen tyrosine kinase. SYK contains two Src homology 2 domains and phosphorylation of the two ITAM tyrosines allows for binding of SYK to the ITAMs of CD79a and CD79b via phosphotyrosine-SH2 interactions. Once bound, SYK phosphorylates several proteins in the downstream signaling pathway as well as neighboring ITAM tyrosines resulting in signal propagation and amplification. In addition to ITAM phosphorylation, the phosphorylation of a non-ITAM tyrosine in the C-terminus of CD79a creates a docking site for the SH2 containing adaptor protein BLNK. BLNK then undergoes receptormediated phosphorylation by SYK, an event causing BLNK to organize the assembly and activation of a multicomponent receptor-retained signalosome responsible for triggering second messenger pathways in the B-cell. Here we used NMR spectroscopy and chemical shift analysis to examine the secondary structure propensity of CD79a and CD79b in their non-phosphorylated and phosphorylated states and to examine how tyrosine phosphorylation affects the secondary structure propensity. A subscript letter P is used throughout this text to indicate the phosphorylated state. CD79a and CD79b were phosphorylated in vitro using the Src family kinase Fyn. The phosphorylated tyrosines were identified through analysis of changes of backbone chemical shifts in the vicinity of the affected sites. Our experiments shows that in their non-phosphorylated states CD79a and CD79b have helical propensity in regions centered on, or close by the C-terminal ITAM tyrosines. The helical propensity of these regions is affected by phosphorylation. For CD79b, the helicity is AQ4 increased while for CD79a a decrease in helicity is observed. Chemical shifts are routinely used to study the structure of folded as well as intrinsically disordered proteins. The deviations of chemical shifts from their anticipated random coil values can be used to examine secondary structure propensity. These deviations are known as secondary chemical shifts and are defined as where d is the observed chemical shift and drc is the random coil chemical shift. Positive Ca secondary chemical shift values indicate prevalence of a-helical structure, while negative values point to preference towards b-strand or extended structure.