Cytoskeletal Signaling

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The MCF2/Dbl proto-oncogene product is the founding member of the Dbl family of Rho guanine nucleotide exchange factors (GEFs) that are characterized by their Dbl homology (DH) domain (1). GEFs stimulate the formation of the active, GTP-bound form of small GTPases such as Rho, Rac and Cdc42, signaling to various downstream molecules and regulating diverse cell functions. While the overexpressed, full-length Dbl gene has transforming activity (2), mutations resulting in truncated Dbl cause the protein to become highly oncogenic. This truncated form of Dbl, which lacks the amino-terminal 497 amino acids, has constitutive GEF activity (3) and is more stable than the full-length variant (4), allowing for increased signaling to downstream effector molecules.Dbl interacts with ezrin, a member of the ezrin/radixin/moesin (ERM) family of proteins that links the plasma membrane to the actin cytoskeleton. Dbl interacts with ezrin in lipid microdomains, which leads to Cdc42 activation and the regulation of processes such as filopodia formation and cell polarity (5,6). Dbl localization and biological activities are regulated in part by phosphatidylinositol 3-kinase (PI3K) (7). Dbl is also involved in cell survival and inhibits apoptosis through induction of Akt phosphorylation at Thr308 (8).

1. Zheng, Y. (2001) Trends Biochem Sci 26, 724-32.
2. Ron, D. et al. (1988) EMBO J 7, 2465-73.
3. Hart, M.J. et al. (1991) Nature 354, 311-4.
4. Kamynina, E. et al. (2007) Mol Cell Biol 27, 1809-22.
5. Batchelor, C.L. et al. (2007) Cell Cycle 6, 353-63.
6. Prag, S. et al. (2007) Mol Biol Cell 18, 2935-48.
7. Vanni, C. et al. (2006) Cell Cycle 5, 2657-65.
8. Morley, S. et al. (2007) Cell Signal 19, 211-8.

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MCF2/Dbl Antibody

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