YAP regulation by Angiomotin is either positive or negative remains a mystery. Now a study appearing in eLife provides new insights into this question. Multi-cellular organisms consist of more than one cell. All species of animals are multi-cellular. But how do cells in animals know when and where to grow and divide? Individual cells communicate with each other and their surrounding environment through a variety of signaling pathways. One such pathway is called Hippo-YAP pathway, which stimulates cells to grow and therefore controls organ size. Dysregulation of the Hippo-YAP pathway contributes to cancer development. A better understanding of how this pathway is regulated could aid in development new drugs for cancer. A protein called Amot (Angiomotin) has been identified as a component of the Hippo-YAP pathway. But exactly how the protein regulates this pathway remains elusive. According to a new study led by The Scripps Research Institute, Klinikum rechts der Isar and Technische Universität München, the function of Amot is dependent on its phosphorylation state. Phosphorylation is a chemical process in which a phosphate group is added to a molecule. Main findings of the study are that that adding a phosphate group to Amot causes the protein to inhibit cell proliferation, while removing a phosphate group causes it to promote cell proliferation, thus increasing cancer cell growth. YAP (Yes-associated protein) is a protein that acts as a transcriptional regulator. Previous studies have linked YAP with many types of cancer, making YAP a promising target for cancer treatment. YAP is a downstream nuclear effector of the Hippo signaling pathway, which is important in cell proliferation and regeneration. Due to its great importance, YAP is strictly regulated by various regulatory systems. There are conflicting reports about the role of Amot in regulating the Hippo-YAP pathway. Some studies suggest that Amot has a YAP-inhibitory function, while others indicate that Amot is important for YAP activity. Now, the new study identified a complex comprised of Amot, YAP, and a third protein called Merlin. When Amot is phosphorylated, the complex is localized at the plasma membrane, where it inhibits cell proliferation. When Amot is hypophosphorylated, the complex is localized in the nucleus, where it facilitates YAP-dependent cell proliferation. Taken together, the results demonstrate that Amot's activities depend on phosphorylation. The study illustrates a mechanism to explain the previous conflicting observations of Amot’s role. (Amot, YAP, Merlin, and other proteins like Recombinant Glp1r can be offered by Cusabio.) Researchers of the study include Susana Moleirinho, Sany Hoxha, Vinay Mandati, Graziella Curtale, Scott Troutman, and Joseph Kissil at The Scripps Research Institute in the United States, and Ursula Ehmer at Technische Universität München in Germany.
