Evidence that the lipid phosphatase SHIP-1 regulates T lymphocyte morphology and motility
Harris, S. J., Parry, R. V., Foster, J. G., Blunt, M. D., Wang, A., Marelli-Berg, F., Westwick, J. and Ward, S. G., 2011. Evidence that the lipid phosphatase SHIP-1 regulates T lymphocyte morphology and motility. The Journal of Immunology, 186 (8), pp. 4936-4945.
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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 GSK3 beta, 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. The Journal of Immunology, 2011, 186: 4936-4945.
|Creators||Harris, S. J., Parry, R. V., Foster, J. G., Blunt, M. D., Wang, A., Marelli-Berg, F., Westwick, J. and Ward, S. G.|
|Departments||Faculty of Science > Pharmacy & Pharmacology|
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