Activation of T cells by cross-linking Qa-2, the ped gene product, requires Fyn.
OBJECTIVE
Qa-2, the product of the Ped (preimplantation development) gene, regulates the rate of cell division of preimplantation mouse embryos by an unknown mechanism. Due to the limited availability of preimplantation embryos, T cells were used as a model system to assess the possible roles of Fyn and Lck, and two downstream effectors, PI-3 kinase and Akt, in Qa-2 induced cell proliferation.


METHODS
Resting T cells were stimulated to proliferate by treating with mouse anti-Qa-2 antibody, cross-linking with anti-mouse immunoglobulin, and adding PMA. The effects of kinase inhibitors on this proliferation were studied. Co-immunoprecipitates of T-cell lysates were analyzed for possible associations between Qa-2 and Fyn or Lck. Fyn knockout mice (Fyn-/-) were used to determine whether Fyn is required for T-cell activation induced by cross-linking Qa-2.


RESULTS
An inhibitor of Src family kinases and inhibitors of PI-3 kinase and Akt suppressed proliferation of resting T cells induced by cross-linking Qa-2. Fyn, but not Lck, co-immunoprecipitated with Qa-2. Fyn-/- T cells failed to proliferate in response to Qa-2 cross-linking.


CONCLUSIONS
Fyn, PI-3 kinase, and Akt are required for the activation of T cells by cross-linking Qa-2.
De Fazio
Sally R
SR
Biology Department, Northeastern University, Boston, MA 02115, USA.
Warner
Carol M
CM
D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000378:metabolism; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D000906:Antibodies; D001755:Blastocyst / Q000201:enzymology / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism*; D007136:Immunoglobulins / Q000378:metabolism; D047468:Immunoprecipitation; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009025:Morpholines / Q000494:pharmacology; D009705:Nucleosides / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011724:Pyridazines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D000077191:Wortmannin
D048868:Adaptor Proteins, Signal Transducing; D000730:Androstadienes; D000906:Antibodies; D002867:Chromones; D003432:Cross-Linking Reagents; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; D009025:Morpholines; D009705:Nucleosides; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D051076:Proto-Oncogene Proteins c-fyn; D011724:Pyridazines; D011743:Pyrimidines; D013755:Tetradecanoylphorbol Acetate; D000077191:Wortmannin; C412373:AG 1879; C488733:API-2 nucleoside; C032907:Q surface antigens; C402726:Sh2d2a protein, mouse; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C494960:Fyn protein, mouse