Fine tuning T lymphocytes: a role for the lipid phosphatase SHIP-1.
The phosphoinositide 3-kinase signaling pathway regulates a range of T lymphocyte cellular functions including growth, proliferation, cytokine secretion and survival. Aberrant regulation of phosphoinositide 3-kinase-dependent signaling in T lymphocytes has been implicated in inflammatory and autoimmune diseases. In common with much of the immune system, several mechanisms exist to ensure the pathway is tightly regulated to elicit appropriate responses. One level of control involves the Src homology 2 domain-containing inositol-5-phosphatase-1 (SHIP-1) that modulates phosphoinositide 3-kinase signaling by degrading the key signaling lipid PI(3,4,5)P(3) to PI(3,4)P(2), but also serves as a key scaffolding molecule in the formation of multi-protein complexes. Here we discuss the role of SHIP-1 in regulating T lymphocyte and immune function, as well as its potential as a therapeutic target.
Parry
Richard V
RV
Inflammatory Cell Biology Laboratory, Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UK.
Harris
Stephanie J
SJ
Ward
Stephen G
SG
D000818:Animals; D001327:Autoimmune Diseases / Q000201:enzymology* / Q000276:immunology; D049109:Cell Proliferation; D002470:Cell Survival / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000276:immunology; D000072181:Inositol Polyphosphate 5-Phosphatases; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D018909:src Homology Domains / Q000276:immunology
D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases; C000606430:INPP5D protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases