Molecular Dissection of the SHIP1 Phosphatase

Presenter: Pilar Tosio – Psychology

Faculty Mentor(s): Grace Waddell

Session: (In-Person) Poster Presentation

The 145 kDa lipid phosphatase SHIP1 is a critical component in immune cell signaling pathways and allows hematopoietic cells to undergo chemotaxis. Although the enzymatic role that SHIP1 plays in the dephosphorylation of phosphatidylinositol-3,4,5-phosphate (PI(3,4,5)P) lipids is understood, much remains unknown about the role SHIP1 plays in the excitable signaling network. Using TIRF microscopy, we can observe SHIP1 being recruited to the plasma membrane where the protein can be activated and inactivated. How this lipid phosphatase is being localized to the plasma membrane is not yet understood. We hypothesized that the region responsible for SHIP1 localization exists within the SHIP1 C-terminus. By performing a molecular dissection of the SHIP1 phosphatase, we determined that the last 110 amino acids of SHIP1’s C-terminus is required for SHIP1 to display polarized membrane localization patterns in human neutrophils. This finding has helped to elucidate the biochemical underpinnings of immune cell migratory functions.