DOCK2 mediates T cell receptor-induced activation of Rac2 and IL-2 transcription.
DOCK2, a CDM family protein exclusively found in hematopoietic cells, has been shown to play a role in lymphocyte migration by the regulation of actin cytoskeleton. Although DOCK2 has been shown to induce the activation of Rac1, the regulatory mechanism of Rac2, which is a hematopoietic cell-specific small GTPase, is still unknown. In this study, we examined the role of DOCK2 in the activation of Rac2 in hematopoietic cells. DOCK2 was found to associate with the zeta subunit of the CD3 complex of T cell receptors in Jurkat cells and to activate forced expressed Rac2 in 293T cells. In addition, the stable expression of DOCK2 in Jurkat cells exhibited the elevated activity of endogenous Rac2. Furthermore, the transcriptional activity of interleukin-2 (IL-2) was enhanced in DOCK2-expressing Jurkat cells and the dominant negative form of Rac2 suppressed its elevated IL-2 promoter activity. These results suggest that DOCK2 mediates TCR-dependent activation of Rac2, leading to the regulation of IL-2 promoter activity in T cells.
Nishihara
Hiroshi
H
Laboratory of Molecular and Cellular Pathology, Hokkaido University School of Medicine, N 15, W7, Kita-ku, Sapporo 060-8638, Japan.
Maeda
Masae
M
Tsuda
Masumi
M
Makino
Yoshinori
Y
Sawa
Hirofumi
H
Nagashima
Kazuo
K
Tanaka
Shinya
S
D002352:Carrier Proteins / Q000502:physiology*; D002460:Cell Line; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics*; D019169:Jurkat Cells; D011401:Promoter Regions, Genetic; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D015533:Transcriptional Activation; D020744:rac GTP-Binding Proteins / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein; D000097766:RAC2 GTP-Binding Protein
D002352:Carrier Proteins; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein; D000097766:RAC2 GTP-Binding Protein; C402110:DOCK2 protein, human