ArticleMolecular and cellular biology2001
Oligomerization of DH domain is essential for Dbl-induced transformation.
Article in Molecular and cellular biology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 46 citations in OpenAlex.
- Structural basis for p50RhoGAP BCH domain-mediated regulation of Rho inactivation.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Prediction of Protein-Protein Interactions Between Alsin DH/PH and Rac1 and Resulting Protein Dynamics.Frontiers in molecular neuroscience · 2021Article
- Differential expression of serum proteins in multiple myeloma.Experimental and therapeutic medicine · 2019Article
- Altered oligomeric states in pathogenic ALS2 variants associated with juvenile motor neuron diseases cause loss of ALS2-mediated endosomal function.The Journal of biological chemistry · 2018Article
- Macropinocytosis activated by oncogenic Dbl enables specific targeted delivery of Tat/pDNA nano-complexes into ovarian cancer cells.International journal of nanomedicine · 2018Article
- New insights into the dimerization of small GTPase Rac/ROP guanine nucleotide exchange factors in rice.Plant signaling & behavior · 2015Article
- Intramolecular interactions between the Dbl homology (DH) domain and the carboxyl-terminal region of myosin II-interacting guanine nucleotide exchange factor (MyoGEF) act as an autoinhibitory mechanism for the regulation of MyoGEF functions.The Journal of biological chemistry · 2014Article
- N-terminal Dbl domain of the RhoGEF, Kalirin.Journal of biomolecular NMR · 2012Article
- Dimerization of DOCK2 is essential for DOCK2-mediated Rac activation and lymphocyte migration.PloS one · 2012Article
- The minimal autoinhibited unit of the guanine nucleotide exchange factor intersectin.PloS one · 2010Article
- Modulation of Rho guanine exchange factor Lfc activity by protein kinase A-mediated phosphorylation.Molecular and cellular biology · 2009Article
- Phosphorylation of MyoGEF on Thr-574 by Plk1 promotes MyoGEF localization to the central spindle.The Journal of biological chemistry · 2008Article
- Lsc activity is controlled by oligomerization and regulates integrin adhesion.Molecular immunology · 2008Article
- Overexpression of the Rho-guanine nucleotide exchange factor ECT2 inhibits nuclear translocation of nuclear receptor CAR in the mouse liver.FEBS letters · 2007Article
- The Dbs PH domain contributes independently to membrane targeting and regulation of guanine nucleotide-exchange activity.The Biochemical journal · 2006Article
- Article
- Pleiotropic defects in TCR signaling in a Vav-1-null Jurkat T-cell line.The EMBO journal · 2002Article
- GFScan: a gene family search tool at genomic DNA level.Genome research · 2002Article
- Defective dendrite elongation but normal fertility in mice lacking the Rho-like GTPase activator Dbl.Molecular and cellular biology · 2002Article
- Autoinhibition mechanism of proto-Dbl.Molecular and cellular biology · 2001Article
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Authors and funding
4 authors at 1 institution in 1 country.
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Abstract
The dbl oncogene product (onco-Dbl) is the prototype member of a family of guanine nucleotide exchange factors (GEFs) for Rho GTPases. The Dbl homology (DH) domain of onco-Dbl is responsible for the GEF catalytic activity, and the DH domain, together with the immediately adjacent pleckstrin homology (PH) domain, constitutes the minimum module bearing transforming function. In the present study, we demonstrate that the onco-Dbl protein exists in oligomeric form in vitro and in cells. The oligomerization is mostly homophilic in nature and is mediated by the DH domain. Mutagenesis studies mapped the region involved in oligomerization to the conserved region 2 of the DH domain, which is located at the opposite side of the Rho GTPase interacting surface. Residue His556 of this region, in particular, is important for this activity, since the H556A mutant retained the GEF catalytic capability and the binding activity toward Cdc42 and RhoA in vitro but was deficient in oligomer formation. Consequently, the Rho GTPase activating potential of the H556A mutant was significantly reduced in cells. The focus-forming and anchorage-independent growth activities of onco-Dbl were completely abolished by the His556-to-Ala mutation, whereas the abilities to stimulate cell growth, activate Jun N-terminal kinase, and cause actin cytoskeletal changes were retained by the mutant. The ability of onco-Dbl to oligomerize allowed multiple Rho GTPases to be recruited to the same signaling complex, and such an ability is defective in the H556A mutant. Taken together, these results suggest that oligomerization of onco-Dbl through the DH domain is essential for cellular transformation by providing the means to generate a signaling complex that further augments and/or coordinates its Rho GTPase activating potential.
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