Allosteric Mechanism to Regulate Association of Syk Tyrosine Kinase with B Cell Receptor
As a central player in modulating multiple pathways in B cell signaling, Syk tyrosine kinase interacts with numerous signaling partners. Phosphorylation of Syk on various tyrosine residues regulates Syk protein-protein interactions and, correspondingly, cellular localization of Syk. We have discovered that phosphorylation of one such tyrosine triggers a conformational change, which is proposed to cause dissociation of Syk from the membrane B-cell receptor. Based on heteronuclear relaxation and residual dipolar couplings, phosphorylation is known to affect orientation of two SH2 domains and induces a change in structural order of a linker region; however an exact description of the new conformational state following phosphorylation is unknown, but important to discern because of its functional importance. The talk will describe our interpretation of data from NMR and calorimetry to determine the effects of phosphorylation on domain reorientation and receptor interactions.