title: A non-mitotic role for Aurora kinase A as a direct activator of cell  migration upon interaction with PLD, FAK and Src.
abstract: Timely activation of Aurora kinase A (AURA, also known as AURKA) is vital for centrosome formation and the progression of mitosis. Nonetheless, it is still unclear if and when other cellular functions are activated by AURA. We report here that Src phosphorylates and activates AURA at T288, and AURA also activates focal adhesion kinase (FAK, also known as PTK2), leading to initiation of cell movement. An additional and new way by which AURA is regulated, is by phospholipase D2 (PLD2), which causes AURA activation. In addition, AURA phosphorylates PLD, so both proteins engage in a positive reinforcement loop. AURA and PLD2 form a protein–protein complex and colocalize to cytoplasmic regions in cells. The reason why PLD activates AURA is because of the production of phosphatidic acid by the lipase, which binds directly to AURA, with the region E171–E211 projected to be a phosphatidic-acid-binding pocket. Furthermore, this direct interaction with phosphatidic acid enhances tubulin polymerization and cooperates synergistically with AURA, FAK and Src in yielding a fully effectual cellular migration. Thus, Src and FAK, and PLD and phosphatidic acid are new upstream regulators of AURA that mediate its role in the non-mitotic cellular function of cell migration.
authors.forename: Madhu
authors.initials: M
authors.lastname: Mahankali
authors.forename: Karen M
authors.initials: KM
authors.lastname: Henkels
authors.forename: Francis
authors.initials: F
authors.lastname: Speranza
authors.forename: Julian
authors.initials: J
authors.lastname: Gomez-Cambronero
mesh_terms: D000818:Animals; D064096:Aurora Kinase A / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D002465:Cell Movement / Q000502:physiology*; D002522:Chlorocebus aethiops; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000378:metabolism; D051418:Focal Adhesion Kinase 2 / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology; D062105:Molecular Docking Simulation; D010712:Phosphatidic Acids / Q000096:biosynthesis; D010739:Phospholipase D / Q000378:metabolism*; D010766:Phosphorylation; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D014404:Tubulin / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D010712:Phosphatidic Acids; D034741:RNA, Small Interfering; D014404:Tubulin; D051418:Focal Adhesion Kinase 2; D019061:src-Family Kinases; D064096:Aurora Kinase A; C105606:phospholipase D2; D010739:Phospholipase D