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Evidence that the lipid phosphatase SHIP-1 regulates T lymphocyte morphology and motility.
J Immunol. 2011 Apr 15; 186(8):4936-45.JI

Abstract

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.

Authors+Show Affiliations

Inflammatory Cell Biology Laboratory, Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21402888

Citation

Harris, Stephanie J., et al. "Evidence That the Lipid Phosphatase SHIP-1 Regulates T Lymphocyte Morphology and Motility." Journal of Immunology (Baltimore, Md. : 1950), vol. 186, no. 8, 2011, pp. 4936-45.
Harris SJ, Parry RV, Foster JG, et al. Evidence that the lipid phosphatase SHIP-1 regulates T lymphocyte morphology and motility. J Immunol. 2011;186(8):4936-45.
Harris, S. J., Parry, R. V., Foster, J. G., Blunt, M. D., Wang, A., Marelli-Berg, F., Westwick, J., & Ward, S. G. (2011). Evidence that the lipid phosphatase SHIP-1 regulates T lymphocyte morphology and motility. Journal of Immunology (Baltimore, Md. : 1950), 186(8), 4936-45. https://doi.org/10.4049/jimmunol.1002350
Harris SJ, et al. Evidence That the Lipid Phosphatase SHIP-1 Regulates T Lymphocyte Morphology and Motility. J Immunol. 2011 Apr 15;186(8):4936-45. PubMed PMID: 21402888.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evidence that the lipid phosphatase SHIP-1 regulates T lymphocyte morphology and motility. AU - Harris,Stephanie J, AU - Parry,Richard V, AU - Foster,John G, AU - Blunt,Matthew D, AU - Wang,Amu, AU - Marelli-Berg,Federica, AU - Westwick,John, AU - Ward,Stephen G, Y1 - 2011/03/14/ PY - 2011/3/16/entrez PY - 2011/3/16/pubmed PY - 2011/8/2/medline SP - 4936 EP - 45 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 186 IS - 8 N2 - 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. SN - 1550-6606 UR - https://www.unboundmedicine.com/medline/citation/21402888/Evidence_that_the_lipid_phosphatase_SHIP_1_regulates_T_lymphocyte_morphology_and_motility_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=21402888 DB - PRIME DP - Unbound Medicine ER -