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  • Title: Galpha13 mediates a signal that is essential for proliferation and survival of thymocyte progenitors.
    Author: Coffield VM, Helms WS, Jiang Q, Su L.
    Journal: J Exp Med; 2004 Nov 15; 200(10):1315-24. PubMed ID: 15534370.
    Abstract:
    G protein signaling via the Galpha12 family (Galpha12 and Galpha13) has not been well studied in T cells. To investigate whether Galpha12 and Galpha13 are involved in thymopoiesis, we expressed the regulator of G protein signaling domain of p115RhoGEF to inhibit Galpha12 and Galpha13 during thymopoiesis. Fetal thymus organ cultures seeded with p115DeltaDH-expressing progenitor cells showed impaired thymopoiesis with a block at the CD4-CD8-CD44-CD25+ (DN3) stage. Using Galpha13 or Galpha12 minigenes, we demonstrated that Galpha13, but not Galpha12, is required for thymopoiesis. T progenitor cells expressing p115DeltaDH showed reduced proliferation and increased cell death. T cell receptor stimulation of the fetal thymus organ cultures did not rescue the block. Overexpression of the antiapoptotic gene Bcl2 rescued the defect in DN3 cells and partially rescued T cell development. Therefore, Galpha13-mediated signaling is necessary in early thymocyte proliferation and survival.
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