De Fazio Sally R, Warner Carol M
Biology Department, Northeastern University, Boston, MA 02115, USA.
Am J Reprod Immunol. 2007 Oct;58(4):315-24. doi: 10.1111/j.1600-0897.2007.00503.x.
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.
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.
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.
Fyn, PI-3 kinase, and Akt are required for the activation of T cells by cross-linking Qa-2.
Qa - 2是胚胎植入前发育（Ped）基因的产物，通过未知机制调节小鼠植入前胚胎的细胞分裂速率。由于植入前胚胎数量有限，因此使用T细胞作为模型系统，以评估Fyn和Lck以及两个下游效应分子PI - 3激酶和Akt在Qa - 2诱导的细胞增殖中的可能作用。
通过用小鼠抗Qa - 2抗体处理、与抗小鼠免疫球蛋白交联并添加佛波酯（PMA）来刺激静息T细胞增殖。研究了激酶抑制剂对这种增殖的影响。分析T细胞裂解物的共免疫沉淀产物，以确定Qa - 2与Fyn或Lck之间是否存在可能的关联。使用Fyn基因敲除小鼠（Fyn - / -）来确定Fyn是否是Qa - 2交联诱导的T细胞活化所必需的。
Src家族激酶抑制剂以及PI - 3激酶和Akt抑制剂抑制了Qa - 2交联诱导的静息T细胞增殖。Fyn而非Lck与Qa - 2共免疫沉淀。Fyn - / - T细胞对Qa - 2交联无增殖反应。
Fyn、PI - 3激酶和Akt是Qa - 2交联激活T细胞所必需的。
