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Evidence that the lipid phosphatase SHIP-1 regulates T lymphocyte morphology and motility.

Harris, Stephanie J., Parry, Richard V., Foster, John G., Blunt, Matthew D., Wang, Amu, Marelli-Berg, Federica, Westwick, John and Ward, Stepehn G. 2011. Evidence that the lipid phosphatase SHIP-1 regulates T lymphocyte morphology and motility. Journal of Immunology 186 (8) , pp. 4936-4945. 10.4049/jimmunol.1002350

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SHIP-1 negatively regulates the PI3K pathway in hematopoietic cells and has an emerging role in T lymphocyte biology. PI3K and SHIP can regulate cell migration in leukocytes, particularly in neutrophils, although their role in T cell migration has been less clear. Therefore, we sought to explore the role of SHIP-1 in human CD4+ T lymphocyte cell migration responses to chemoattractants using a lentiviral-mediated expression system and a short hairpin RNA approach. Silencing of SHIP-1 leads to increased basal phosphorylation of protein kinase B/Akt and its substrate GSK3β, as well as an increase in basal levels of polymerized actin, suggesting that SHIP-1 might regulate changes in the cytoskeleton. Accordingly, silencing of SHIP-1 led to loss of microvilli and ezrin/radixin/moesin phosphorylation, which could not be rescued by the PI3K inhibitor Ly294002. There were striking morphological changes, including a loss of microvilli projections, which mirrored changes in wild type cells after stimulation with the chemokine CXCL11. There was no defect in directional T cell migration toward CXCL11 in the SHIP-1–silenced cells but, importantly, there was a defect in the overall basal motility of SHIP-1 knockdown cells. Taken together, these results implicate SHIP-1 as a key regulator of basal PI3K signaling in human CD4+ T lymphocytes with important phosphatase-independent actions, which together are key for maintaining normal morphology and basal motility.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: American Association of Immunologists
ISSN: 0022-1767
Date of Acceptance: 11 February 2011
Last Modified: 12 Mar 2020 11:09

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