TY - JOUR
T1 - DOCK2 mediates T cell receptor-induced activation of Rac2 and IL-2 transcription
AU - Nishihara, Hiroshi
AU - Maeda, Masae
AU - Tsuda, Masumi
AU - Makino, Yoshinori
AU - Sawa, Hirofumi
AU - Nagashima, Kazuo
AU - Tanaka, Shinya
N1 - Funding Information:
We thank Dr. Kazuya Iwabuchi (Hokkaido University, Japan) for useful comments, Dr. M. Lienhard Schmitz (German Cancer Research Center, Germany), and Dr. Arthur Weiss (UCSF, USA) for plasmids. H.N. was supported by a grant of Japan Foundation for Aging and Health. This work was supported in part by a grant from the Ministry of Education, Science, Sports and Culture of Japan.
PY - 2002
Y1 - 2002
N2 - 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 ζ 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.
AB - 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 ζ 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.
KW - DOCK2
KW - Interleukin-2
KW - Rac2
KW - T cell antigen receptor
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U2 - 10.1016/S0006-291X(02)00931-2
DO - 10.1016/S0006-291X(02)00931-2
M3 - Article
C2 - 12176041
AN - SCOPUS:0036384348
SN - 0006-291X
VL - 296
SP - 716
EP - 720
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -