Structural Basis of Feedback Control of Oncogenic Signaling in B-Lymphoid Malignancies

Introduction: Multiple structural elements are known that recruit kinases to sites of active signal transduction (e.g. lipid rafts) within the plasma membrane. For instance, pleckstrin homology (PH) domains and the conserved intracellular loop (CIL) motifs recently discovered by us (Lee et al., Nature 2021) direct kinase molecules (Src, BTK, AKT and PI3K) to large signaling clusters in lipid rafts to amplify normal or oncogenic B-cell signaling. While concepts of site-specific recruitment of kinases to initiate signaling are well established, little is known about spatial control of inhibitory phosphatases and how they are directed to sites of maximal signaling strength.