Immune regulatory functions of DOCK family proteins in health and disease |
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| Authors: | Akihiko Nishikimi Mutsuko Kukimoto-Niino Shigeyuki Yokoyama Yoshinori Fukui |
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| Institution: | 1. Division of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan;2. Research Center for Advanced Immunology, Kyushu University, Fukuoka 812-8582, Japan;3. Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Tokyo 102-0075, Japan;4. RIKEN Systems and Structural Biology Center, Yokohama 230-0045, Japan;5. Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Tokyo 113-0033, Japan |
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| Abstract: | DOCK proteins constitute a family of evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho family of GTPases. Although DOCK family proteins do not contain the Dbl homology domain typically found in GEFs, they mediate the GTP–GDP exchange reaction through DHR-2 domain. Accumulating evidence indicates that the DOCK proteins act as major GEFs in varied biological settings. For example, DOCK2, which is predominantly expressed in hematopoietic cells, regulates migration and activation of leukocytes through Rac activation. On the other hand, it was recently reported that mutations of DOCK8, another member of the DOCK family proteins, cause a combined immunodeficiency syndrome in humans. This article reviews the structure, functions and signaling of DOCK2 and DOCK8, especially focusing on their roles in immune responses. |
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| Keywords: | Migration Activation Leukocytes Small GTPases Guanine nucleotide exchange factors |
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