Areas of Expertise Cell Signaling, Informatics & Proteomics, Molecular Biophyics Proteomics and Signal Transduction Our goal is to discover new mechanisms underlying the regulation and function of cell signaling. A major aim is to develop and apply new methods for protein profiling by mass spectrometry with biochemical and cellular approaches to investigate cellular responses to signaling pathways. A second aim is to examine internal motions in protein kinases, demonstrating coupling between protein dynamics and catalytic function. Wnt5A signaling Wnt5A, which normally controls embryonic body axis formation, is elevated in high-grade melanomas and promotes cell invasion. We discovered a novel protein-organelle complex, which directs lifting and retraction of tail-end plasma membrane during directional cell movement. The complex, named the “Wnt5a receptor-actin-myosin-polarity (WRAMP) structure" involves the MCAM/CD146/MUC18 cell adhesion receptor, which polarizes intracellularly, dynamically recruiting actin and myosin-II to the cell posterior where it triggers membrane retraction and moves cells forward (Fig. 1). Whereas cell polarity studies often focus on events at the cell leading edge, the WRAMP structure shows that signaling at the rear is equally important for directional cell movement.