| Symbol |
DBL |
| Full Name |
DBL Proto-Oncogene, Rho GEF (MCF2) |
| Chromosome |
Xq27.1 |
| NCBI Gene |
9075 |
| Ensembl |
ENSG00000123146 |
| UniProt |
P12931 |
| Diseases |
B-Cell Lymphoma, Prostate Cancer, X-Linked Mental Retardation |
| Expression |
Brain, Spleen, Testis, Lymphoid tissues |
DBL (also known as MCF2) is a proto-oncogene that encodes a Rho guanine nucleotide exchange factor (RhoGEF). DBL was originally identified as an oncogene from a diffuse B-cell lymphoma. The protein functions as a specific activator of Rho GTPases, particularly RhoA, Rac1, and Cdc42, which are critical regulators of the actin cytoskeleton.
DBL is a prototypic RhoGEF that catalyzes the exchange of GDP for GTP on Rho GTPases:
- RhoA activation — leads to stress fiber formation and contractility
- Rac1 activation — promotes lamellipodia and membrane ruffling
- Cdc42 activation — induces filopodia formation
In neurons, DBL and related RhoGEFs regulate:
- Axon guidance — Rho GTPase signaling directs growth cone steering
- Dendritic morphogenesis — branching and spine formation
- Synapse formation — postsynaptic density organization
- Neuronal migration — cytoskeletal dynamics during development
DBL participates in several signaling cascades:
- G-protein coupled receptor (GPCR) signaling
- Receptor tyrosine kinase signaling
- Integrin-mediated adhesion signaling
- Wnt/planar cell polarity signaling
DBL was originally discovered as an oncogene in diffuse B-cell lymphoma. Dysregulation contributes to:
- B-cell lymphomas — overexpression and genomic rearrangements
- Prostate cancer — associated with metastatic progression
- Breast cancer — expression correlates with aggressiveness
Given its role in neuronal development:
- X-linked mental retardation — rare variants may affect cognitive development
- Neurodevelopmental syndromes — related to Rho GTPase signaling
The Rho GTPase pathways are relevant to:
- Alzheimer's disease — actin cytoskeletal abnormalities
- Parkinson's disease — dopamine neuron survival pathways
- Huntington's disease — mutant huntingtin affects Rho GTPase signaling
- Cerione et al., DBL as a Rho GEF (1994)
- Bishop et al., Rho GTPases in neuronal development (2000)
- Hall & Lalli, Rho GTPases in neuronal function (2010)
- Cerione et al., DBL as a Rho-specific guanine nucleotide exchange factor (1994)
- Rossman et al., Rho GTPase signaling by Dbl family guanine nucleotide exchange factors (2005)
- Hall & Lalli, Rho GTPases in neuronal development and function (2010)
- Nakayama et al., DBL mutations in cancer (2012)
- Stankiewicz & Linseman, Rho family GTPases in synaptic plasticity and neurological disorders (2014)
- Liu et al., DBL in neuronal morphogenesis (2016)
- Zhang &Scopeci, Rho GTPase signaling in neurodegeneration (2018)
- Madigan et al., Dbl family GEFs in neurological disease (2019)