Dedicator of Cytokinesis 2 in Cell Signaling Regulation and Disease Development
1Department of Physiology and Pharmacology, University of Georgia, Athens, Georgia.
Abstract:
Dedicator of cytokinesis 2 (DOCK2) is a CDM family protein containing DOCK homology region (DHR)-1 and DHR-2, Src-homology 3 (SH3) domain, and C-terminal polybasic amino acid cluster. The CDM family consists of 11 mammalian members and is classified into four subfamilies, the DOCK-A, -B, -C, and -D. DOCK2 is a member of DOCK-A subfamily and an atypical guanine exchange factor regulating the loading of GTP to activate Rac. It is primarily found in peripheral blood, spleen, and thymus and mainly expressed in lymphocytes and macrophages of various organs. DOCK2 is also expressed in microglial in brain and is induced in neointima smooth muscle following vascular injury. Functionally, DOCK2 is involved in cell motility, polarity, adhesion, proliferation, and apoptosis. It is essential for lymphocyte migration and activation as well as neutrophil chemotaxis. DOCK2 also regulates the differentiation of natural killer T cells, type 2 T helper cells, and plasmacytoid dendritic cells. In addition, it is important for the growth of B cell lymphoma and prostate cancer cells. Deletion of DOCK2 enables long-term cardiac allograft survival. Moreover, DOCK2 is associated with the Alzheimer Disease, HIV development, and the early-onset of invasive infections. Recently, we found that DOCK2 plays a critical role in SMC phenotypic modulation and vascular remodeling. In this review, we will briefly summarize recent advancement of DOCK2 function. J. Cell. Physiol. 232: 1931-1940, 2017. © 2016 Wiley Periodicals, Inc.
Insights
Dedicator of cytokinesis 2 (DOCK2) is a guanine exchange factor crucial for immune cell function and vascular remodeling. Its dysregulation is linked to diseases like Alzheimer
Area of Science:
- Cell Biology
- Immunology
- Molecular Biology
Background:
- Dedicator of cytokinesis 2 (DOCK2) is a CDM family protein and atypical guanine nucleotide exchange factor.
- DOCK2 regulates GTP loading to activate Rac, impacting cellular processes.
- It is primarily expressed in immune cells like lymphocytes and macrophages, and in brain microglia.
Purpose of the Study:
- To review recent advancements in understanding DOCK2 function.
- To highlight DOCK2's roles in cell motility, polarity, adhesion, proliferation, and apoptosis.
- To summarize DOCK2's involvement in immune cell differentiation and disease pathogenesis.
Main Methods:
- This is a review article, synthesizing existing research findings.
- Literature search and analysis of studies on DOCK2 function and its implications.
Main Results:
- DOCK2 is essential for lymphocyte migration, activation, and neutrophil chemotaxis.
- It influences the differentiation of various immune cell types, including NK T cells and dendritic cells.
- DOCK2 is implicated in B cell lymphoma, prostate cancer, vascular remodeling, Alzheimer's disease, HIV, and infections.
Conclusions:
- DOCK2 plays a critical role in immune responses and vascular homeostasis.
- Dysregulation of DOCK2 is associated with diverse pathological conditions.
- Further research into DOCK2 function may reveal therapeutic targets for various diseases.
Related Concept Videos
02:02Meiosis II
The timing and cell division patterns of meiosis differ between males and females. In male meiosis, the centrosomes are part of the formation of the meiotic spindle. However, in oocytes, including that of humans, Drosophila,...
02:39Positive Regulator Molecules
01:45Positive Regulator Molecules
02:34Inhibition of Cdk Activity
02:34Inhibition of CDK Activity
01:27Molecular Factors Affecting Cell Division
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...