Insights from DOCK2 in cell function and pathophysiology

Abstract

Dedicator of cytokinesis 2 (DOCK2) can activate the downstream small G protein Rac and regulate cytoskeletal reorganization. DOCK2 is essential for critical physiological processes such as migration, activation, proliferation, and effects of immune cells, including lymphocytes, neutrophils, macrophages, and dendritic cells. For example, DOCK2 is involved in the development and activation of T and B lymphocytes by affecting synapse formation and inhibiting the development of the Th2 lineage by downregulating IL-4Rα surface expression. Not only that, DOCK2 may be a molecular target for controlling cardiac transplant rejection and Alzheimer’s disease (AD). Patients with defects in the DOCK2 gene also exhibit a variety of impaired cellular functions, such as chemotactic responses of lymphocytes and reactive oxygen species (ROS) production by neutrophils. To date, DOCK2 has been shown to be involved in the development of various diseases, including AD, pneumonia, myocarditis, colitis, tumors, etc. DOCK2 plays different roles in these diseases and the degree of inflammatory response has a different impact on the progression of disease. In this paper, we present a review of recent advances in the function of DOCK2 in various immune cells and its role in various diseases.

Integrative network analysis of transcriptomics data reveals potential prognostic biomarkers for colorectal cancer

“…DOCK2 (Dedicator of Cytokinesis 2) is reported to play a crucial role in the regulation and activation of T cells and NK cells. Notably, our findings align with previous reports identifying DOCK2 as the most frequently mutated gene in CRC 43 . These observations suggest the important role of PTPRC in pathway cross‐talks in the CRC state.…”

“…Notably, our findings align with previous reports identifying DOCK2 as the most frequently mutated gene in CRC. 43 These observations suggest the important role of PTPRC in pathway cross-talks in the CRC state. Our analysis also found the cross-talk of TCR signaling pathway with the MAPK signaling pathways in the CRC state.…”

Transcriptomic analysis of the ocular posterior segment completes a cell atlas of the human eye

“…Six clusters (C4, 7, 9, 24, 25, and 30) expressed markers of immune cells including PTPRC and DOCK2 ( 47 , 48 ) ( Fig. 2 C ).…”

Transinteractome analysis reveals distinct niche requirements for isotype‐based plasma cell subsets in the bone marrow

“…Wls regulates Wnt protein trafficking that has been shown to contribute to PC resistance to bortezomib [36, 37], whereas Clec2i was shown to be up‐regulated in LAG3 + Il‐10 producing PCs [38]. In addition, Dock2 and Plek implicated in lymphocyte activation/migration [39–41], as well as Ddit3 encoding the Chop protein [42], were more expressed in IgM + PCs than in IgG + PCs. Conversely, IgG + PCs expressed more Acp2 , implicated in lysosomal acidification, than IgA + PCs [43] (Supporting Information Fig.…”