DOCK2 regulates cell proliferation through Rac and ERK activation in B cell lymphoma

Wang, Lei; Nishihara, Hiroshi; Kimura, Taichi; Kato, Yasutaka; Tanino, Mishie; Nishio, Mitsufumi; Obara, Masato; Endo, Tomoyuki; Koike, Takao; Tanaka, Shinya

doi:10.1016/j.bbrc.2010.03.148

Cited by 34 publications

(36 citation statements)

References 20 publications

(11 reference statements)

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“…DOCK2 (encoded by DOCK2 gene), a member of the CDM protein family, is involved in remodeling of the actin cytoskeleton required for lymphocyte migration through the activation of RAC. 28 It has been proved that DOCK2 regulated cell motility and cytokine production via the activation of Rac in mammalian hematopoietic cells and had a pivotal role in the modulation of the immune system. 28 Huang et al 29 proved that upregulation of immune defense-associated genes was involved in the biologic behavior of PA.…”

Section: Discussionmentioning

confidence: 99%

“…28 It has been proved that DOCK2 regulated cell motility and cytokine production via the activation of Rac in mammalian hematopoietic cells and had a pivotal role in the modulation of the immune system. 28 Huang et al 29 proved that upregulation of immune defense-associated genes was involved in the biologic behavior of PA. Hence, DOCK2 may have a key role in PA. On the other hand, DNA methylation is important for brain development as genetic diseases based on defects therein result in mental retardation, especially in gliomas.…”

Section: Discussionmentioning

confidence: 99%

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Screening genes crucial for pediatric pilocytic astrocytoma using weighted gene coexpression network analysis combined with methylation data analysis

Zhao

Cai

et al. 2014

Cancer Gene Ther

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To identify novel genes associated with pediatric pilocytic astrocytoma (PA) for better understanding the molecular mechanism underlying the pediatric PA pathogenesis. Gene expression profile data of GSE50161 and GSE44971 and the methylation data of GSE44684 were downloaded from Gene Expression Omnibus. The differentially expressed genes (DEGs) between PA and normal control samples were screened using the limma package in R, and then used to construct weighted gene coexpression network (WGCN) using the WGCN analysis (WGCNA) package in R. Significant modules of DEGs were selected using the clustering analysis. Function enrichment analysis of the DEGs in significant modules were performed using the WGCNA package and clusterprofiler package in R. Correlation between methylation sites of DEGs and PA was analyzed using the CpGassoc package in R. Totally, 3479 DEGs were screened in PA samples. Thereinto, 3424 DEGs were used to construct the WGCN. Several significant modules of DEGs were selected based on the WGCN, in which the turquoise module was positively related to PA, whereas blue module was negatively related to PA. DEGs (for example, DOCK2 (dedicator of cytokinesis 2), DOCK8 and FCGR2A (Fc fragment of IgG, low affinity IIa)) in blue module were mainly involved in Fc gamma R-mediated phagocytosis pathway and natural killer cell-mediated cytotoxicity pathway. Methylations of 14 DEGs among the top 30 genes in blue module were related to PA. Our data suggest that DOCK2, DOCK8 and FCGR2A may represent potential therapeutic targets in PA that merits further investigation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Screening genes crucial for pediatric pilocytic astrocytoma using weighted gene coexpression network analysis combined with methylation data analysis

Zhao

Cai

et al. 2014

Cancer Gene Ther

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“…RNF43 encodes an E3 ubiquitin ligase that is overexpressed in colorectal cancer28 and mutated in ovarian cancer. DOCK2 encodes a member of the CDM protein family and regulates cell motility and cytokine production through the activation of Rac in mammalian hematopoietic cells29. DOCK2 is mutated in ovarian and pancreatic cancers.…”

Section: Discussionmentioning

confidence: 99%

Whole-exome sequencing uncovers frequent GNAS mutations in intraductal papillary mucinous neoplasms of the pancreas

Furukawa

Kuboki

Tanji

et al. 2011

Sci Rep

389

340

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Intraductal papillary mucinous neoplasm (IPMN) is a common pancreatic cystic neoplasm that is often invasive and metastatic, resulting in a poor prognosis. Few molecular alterations unique to IPMN are known. We performed whole-exome sequencing for a primary IPMN tissue, which uncovered somatic mutations in KCNF1, DYNC1H1, PGCP, STAB1, PTPRM, PRPF8, RNASE3, SPHKAP, MLXIPL, VPS13C, PRCC, GNAS, KRAS, RBM10, RNF43, DOCK2, and CENPF. We further analyzed GNAS mutations in archival cases of 118 IPMNs and 32 pancreatic ductal adenocarcinomas (PDAs), which revealed that 48 (40.7%) of the 118 IPMNs but none of the 32 PDAs harbored GNAS mutations. G-protein alpha-subunit encoded by GNAS and its downstream targets, phosphorylated substrates of protein kinase A, were evidently expressed in IPMN; the latter was associated with neoplastic grade. These results indicate that GNAS mutations are common and specific for IPMN, and activation of G-protein signaling appears to play a pivotal role in IPMN.

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“…In addition, NSC23766, a specific Rac inhibitor, significantly decreases the ERK phosphorylation level in WT Ramos cells. In vivo tumorigenesis assay show that the tumor sizes of subcutaneous xenografts of DOCK2‐shRNA transfected Ramos cells are significantly smaller than the control Ramos cells (Wang et al, ). Therefore, DOCK2‐Rac may be an alternative target for B lymphoma therapy.…”

Section: Dock2 Cellular Functionmentioning

confidence: 99%

Dedicator of Cytokinesis 2 in Cell Signaling Regulation and Disease Development

Guo

Chen

2017

Journal Cellular Physiology

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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.

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DOCK2 regulates cell proliferation through Rac and ERK activation in B cell lymphoma

Cited by 34 publications

References 20 publications

Screening genes crucial for pediatric pilocytic astrocytoma using weighted gene coexpression network analysis combined with methylation data analysis

Screening genes crucial for pediatric pilocytic astrocytoma using weighted gene coexpression network analysis combined with methylation data analysis

Whole-exome sequencing uncovers frequent GNAS mutations in intraductal papillary mucinous neoplasms of the pancreas

Dedicator of Cytokinesis 2 in Cell Signaling Regulation and Disease Development

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