ArticleThe Journal of biological chemistry2013
Deciphering the molecular and functional basis of Dbl family proteins: a novel systematic approach toward classification of selective activation of the Rho family proteins.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 108 citations in OpenAlex.
- The Rho guanine-nucleotide exchange factor P-Rex2 exhibits structural and regulatory features distinct from the related RhoGEF P-Rex1.The Journal of biological chemistry · 2026Article
- Profiling Ten RHO GTPases in Myeloid Malignancies Reveals Distinct Expression Patterns and Prognostic Associations.Cancer medicine · 2026Article
- P-Rex2 exhibits unique structural features and regulatory mechanisms distinct from the closely related RhoGEF P-Rex1.bioRxiv : the preprint server for biology · 2026Article
- New insights into the classification of the RAC1 P29S hotspot mutation in melanoma as an oncogene.Cancer gene therapy · 2025Article
- Tensins in Cancer: Integration of Their Domain Functions, Context-Dependent Regulation and Biomarker Potential.Biology · 2025Review
- Regulation of Rho guanine nucleotide exchange factor 3 by phosphorylation in the PH domain.iScience · 2025Article
- Modulating PAK1: Accessory Proteins as Promising Therapeutic Targets.Biomolecules · 2025Review
- Roles of small GTPases in cardiac hypertrophy (Review).Molecular medicine reports · 2024Review
- Article
- Single-cell long-read sequencing-based mapping reveals specialized splicing patterns in developing and adult mouse and human brain.Nature neuroscience · 2024Article
- RHOAScience signaling · 2023Article
- Genomic and Reverse Translational Analysis Discloses a Role for Small GTPase RhoA Signaling in the Pathogenesis of Schizophrenia: Rho-Kinase as a Novel Drug Target.International journal of molecular sciences · 2023Review
- A Systematic Compilation of Human SH3 Domains: A Versatile Superfamily in Cellular Signaling.Cells · 2023Review
- Role of RhoG as a regulator of cellular functions: integrating insights on immune cell activation, migration, and functions.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Review
- The potential therapeutic roles of Rho GTPases in substance dependence.Frontiers in molecular neuroscience · 2023Article
- Structural Dynamics of P-Rex1 Complexed with Natural Leads Establishes the Protein as an Attractive Target for Therapeutics to Suppress Cancer Metastasis.BioMed research international · 2023Article
- Article
- Fission Yeast Rho1p-GEFs: From Polarity and Cell Wall Synthesis to Genome Stability.International journal of molecular sciences · 2022Review
- Characterization and computational simulation of human Syx, a RhoGEF implicated in glioblastoma.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Identification of Arhgef12 and Prkci as genetic modifiers of retinal dysplasia in the Crb1rd8 mouse model.PLoS genetics · 2022Article
15 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The diffuse B-cell lymphoma (Dbl) family of the guanine nucleotide exchange factors is a direct activator of the Rho family proteins. The Rho family proteins are involved in almost every cellular process that ranges from fundamental (e.g. the establishment of cell polarity) to highly specialized processes (e.g. the contraction of vascular smooth muscle cells). Abnormal activation of the Rho proteins is known to play a crucial role in cancer, infectious and cognitive disorders, and cardiovascular diseases. However, the existence of 74 Dbl proteins and 25 Rho-related proteins in humans, which are largely uncharacterized, has led to increasing complexity in identifying specific upstream pathways. Thus, we comprehensively investigated sequence-structure-function-property relationships of 21 representatives of the Dbl protein family regarding their specificities and activities toward 12 Rho family proteins. The meta-analysis approach provides an unprecedented opportunity to broadly profile functional properties of Dbl family proteins, including catalytic efficiency, substrate selectivity, and signaling specificity. Our analysis has provided novel insights into the following: (i) understanding of the relative differences of various Rho protein members in nucleotide exchange; (ii) comparing and defining individual and overall guanine nucleotide exchange factor activities of a large representative set of the Dbl proteins toward 12 Rho proteins; (iii) grouping the Dbl family into functionally distinct categories based on both their catalytic efficiencies and their sequence-structural relationships; (iv) identifying conserved amino acids as fingerprints of the Dbl and Rho protein interaction; and (v) defining amino acid sequences conserved within, but not between, Dbl subfamilies. Therefore, the characteristics of such specificity-determining residues identified the regions or clusters conserved within the Dbl subfamilies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.