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Gene Review

Mcf2  -  mcf.2 transforming sequence

Mus musculus

Synonyms: B230117G22Rik, Dbl, Mcf-2
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Disease relevance of Mcf2

  • However, the N-terminus of Mcf2 shows significant similarity to the type-III secreted effector HrmA from the plant pathogen Pseudomonas syringae and no similarity to the N-terminus of Mcf1 [1].
  • Here we show that E. coli expressing Mcf2 can, like E. coli expressing Mcf1, kill insects [1].
  • The Dbl homology domain of BCR is not a simple spacer in P210BCR-ABL of the Philadelphia chromosome [2].
  • Here we show that Evi24, a common site of retroviral integration in AKXD B cell and BXH-2 myeloid leukemias, contains a novel Dbl family guanine nucleotide exchange factor gene [3].
  • However, control studies with fibroblast lines and UV-induced fibrosarcoma cells unexpectedly revealed a high susceptibility to lysis by Dbl cells among certain Ia- cell lines [4].

High impact information on Mcf2

  • Receptor-initiated stimulation of Dbl protein Vav exchange activity involves tyrosine phosphorylation [5].
  • Expression of this mutant in NIH 3T3 fibroblasts causes cellular transformation, mimicking many of the characteristics of cells transformed by the Dbl oncoprotein, a known guanine nucleotide exchange factor for Cdc42 [6].
  • Vav contains an array of structural motifs that include Src-homology domains SH2/SH3 and regions of homology to the guanine-nucleotide-exchange protein Dbl, pleckstrin and protein kinase C (refs 5-9) [7].
  • In addition, we show that overexpression of Vav-2 in cytotoxic lymphocytes enhances cellular cytotoxicity, and this enhancement requires a functional Dbl homology and Src homology 2 domain [8].
  • Comparison of BrdU uptake in Ig- and Dbl-Tg mice indicated that B cells from Dbl-Tg mice were renewed at a much higher rate (50% renewal times of 0.64 vs. 3.4 wk for total B cells, and 1.2 vs. 5.0 wk for mature B200hi/HSAlo cells from Dbl- and Ig-transgenic mice, respectively) [9].

Biological context of Mcf2


Anatomical context of Mcf2

  • However, in distinct populations of Dbl-null cortical pyramidal neurons, the length of dendrites was significantly reduced, suggesting a role for Dbl in dendrite elongation [12].
  • Dbl is specifically expressed in brain and gonads, but its in vivo functions are largely unknown [12].
  • Further, these mutants lost both the plasma membrane targeting and the transforming activities, contrary to the PH mutants of onco-Dbl that retained the exchange activity both in vitro and in vivo and showed significant, but partially, reduced transforming activity [14].
  • Regulation of proto-Dbl by intracellular membrane targeting and protein stability [14].
  • Transduction of IBP-deficient T cells with a WT IBP protein, but not with an IBP mutant lacking the Dbl-like domain required for Rho GTPase activation, rescues the cytoskeletal defects exhibited by these cells [15].

Associations of Mcf2 with chemical compounds

  • Dbl-related oncoproteins are guanine nucleotide exchange factors (GEFs) specific for Rho guanosine triphosphatases (GTPases) and invariably possess tandem Dbl (DH) and pleckstrin homology (PH) domains [16].
  • The NH2-terminal region of Ras-GRF2 is predicted to contain features common to various signaling proteins including two pleckstrin homology domains and a Dbl homology region [17].
  • Surprisingly, in contrast to observations with other Dbl family proteins, we found that mutation of the invariant tryptophan residue in the PH domain did not impair DeltaN-Ect2 DH/PH/C transforming activity [18].
  • We have purified and identified a 32-kDa protein interacting with the Dbl oncogene homology domain of mSos1(Sos-DH) from rat brains by glutathione S-transferase-Sos-DH affinity chromatography [19].
  • The 85-kDa betaPix-a protein contains an Src homology 3 domain, the tandem Dbl homology and Pleckstrin homology domains, a proline-rich region, and a GIT1-binding domain [20].

Physical interactions of Mcf2

  • Dbl is complexed with Hsc70 in transfected cells, as well as in native mouse brain extracts [21].

Other interactions of Mcf2

  • Despite this short distance we were able to order Mcf-2 and Cf-9 relative to one another and other genes in this region [10].
  • Dbl is the prototype of a large family of GDP-GTP exchange factors for small GTPases of the Rho family [12].
  • Defective dendrite elongation but normal fertility in mice lacking the Rho-like GTPase activator Dbl [12].
  • We propose that Hsc70 attenuates Dbl activity by maintaining an inactive conformation in which the amino terminus is "folded over" the catalytic DH-PH domain [21].
  • This interaction modulates both the GEF activity and the targeting to the plasma membrane of onco-Dbl [14].

Analytical, diagnostic and therapeutic context of Mcf2

  • Comparative sequence analysis suggests that a subset of Dbl-family proteins will utilize their PH domains similarly to Dbs [16].
  • Site-directed mutagenesis was used to examine the role of the Dbl and pleckstrin homology (PH) domains located in the N terminus [22].
  • The DH domain was not tyrosine-phosphorylated in vitro, nor could we find any differences in peptide mapping between in vitro phosphorylated P210/WT and P210/Dbl [2].
  • To gain insights into Dbl oncogene-induced transformation we compared gene expression profiles between Dbl oncogene-transformed and parental NIH3T3 cells by cDNA microarray [23].


  1. The insecticidal toxin makes caterpillars floppy 2 (Mcf2) shows similarity to HrmA, an avirulence protein from a plant pathogen. Waterfield, N.R., Daborn, P.J., Dowling, A.J., Yang, G., Hares, M., ffrench-Constant, R.H. FEMS Microbiol. Lett. (2003) [Pubmed]
  2. The Dbl homology domain of BCR is not a simple spacer in P210BCR-ABL of the Philadelphia chromosome. Kin, Y., Li, G., Shibuya, M., Maru, Y. J. Biol. Chem. (2001) [Pubmed]
  3. Activation of clg, a novel dbl family guanine nucleotide exchange factor gene, by proviral insertion at evi24, a common integration site in B cell and myeloid leukemias. Himmel, K.L., Bi, F., Shen, H., Jenkins, N.A., Copeland, N.G., Zheng, Y., Largaespada, D.A. J. Biol. Chem. (2002) [Pubmed]
  4. The syngeneic T-T lymphocyte reaction (STTLR). II. Induction of primary T anti-T cell cytotoxic responses in vitro in T cell cultures stimulated with syngeneic self-reactive T cells. Suzuki, H., Quintáns, J. J. Mol. Cell. Immunol. (1986) [Pubmed]
  5. Structural basis for relief of autoinhibition of the Dbl homology domain of proto-oncogene Vav by tyrosine phosphorylation. Aghazadeh, B., Lowry, W.E., Huang, X.Y., Rosen, M.K. Cell (2000) [Pubmed]
  6. The gamma-subunit of the coatomer complex binds Cdc42 to mediate transformation. Wu, W.J., Erickson, J.W., Lin, R., Cerione, R.A. Nature (2000) [Pubmed]
  7. Defective antigen receptor-mediated proliferation of B and T cells in the absence of Vav. Tarakhovsky, A., Turner, M., Schaal, S., Mee, P.J., Duddy, L.P., Rajewsky, K., Tybulewicz, V.L. Nature (1995) [Pubmed]
  8. The Rho family guanine nucleotide exchange factor Vav-2 regulates the development of cell-mediated cytotoxicity. Billadeau, D.D., Mackie, S.M., Schoon, R.A., Leibson, P.J. J. Exp. Med. (2000) [Pubmed]
  9. Reduced life span of anergic self-reactive B cells in a double-transgenic model. Fulcher, D.A., Basten, A. J. Exp. Med. (1994) [Pubmed]
  10. Localization of the mouse Mcf-2 (Dbl) protooncogene within a conserved linkage group on the mouse X chromosome. Grant, S.G., Mattei, M.G., Galland, F., Stephenson, D.A., Keitz, B.T., Birnbaum, D., Chapman, V.M. Cytogenet. Cell Genet. (1990) [Pubmed]
  11. Restriction and complexity of Mcf2 proto-oncogene expression. Galland, F., Pirisi, V., de Lapeyriere, O., Birnbaum, D. Oncogene (1991) [Pubmed]
  12. Defective dendrite elongation but normal fertility in mice lacking the Rho-like GTPase activator Dbl. Hirsch, E., Pozzato, M., Vercelli, A., Barberis, L., Azzolino, O., Russo, C., Vanni, C., Silengo, L., Eva, A., Altruda, F. Mol. Cell. Biol. (2002) [Pubmed]
  13. Ezrin function is required for ROCK-mediated fibroblast transformation by the Net and Dbl oncogenes. Tran Quang, C., Gautreau, A., Arpin, M., Treisman, R. EMBO J. (2000) [Pubmed]
  14. Regulation of proto-Dbl by intracellular membrane targeting and protein stability. Vanni, C., Mancini, P., Gao, Y., Ottaviano, C., Guo, F., Salani, B., Torrisi, M.R., Zheng, Y., Eva, A. J. Biol. Chem. (2002) [Pubmed]
  15. Loss of IRF-4-binding protein leads to the spontaneous development of systemic autoimmunity. Fanzo, J.C., Yang, W., Jang, S.Y., Gupta, S., Chen, Q., Siddiq, A., Greenberg, S., Pernis, A.B. J. Clin. Invest. (2006) [Pubmed]
  16. A crystallographic view of interactions between Dbs and Cdc42: PH domain-assisted guanine nucleotide exchange. Rossman, K.L., Worthylake, D.K., Snyder, J.T., Siderovski, D.P., Campbell, S.L., Sondek, J. EMBO J. (2002) [Pubmed]
  17. Cloning and characterization of Ras-GRF2, a novel guanine nucleotide exchange factor for Ras. Fam, N.P., Fan, W.T., Wang, Z., Zhang, L.J., Chen, H., Moran, M.F. Mol. Cell. Biol. (1997) [Pubmed]
  18. Requirement for C-terminal sequences in regulation of Ect2 guanine nucleotide exchange specificity and transformation. Solski, P.A., Wilder, R.S., Rossman, K.L., Sondek, J., Cox, A.D., Campbell, S.L., Der, C.J. J. Biol. Chem. (2004) [Pubmed]
  19. The Sos1-Rac1 signaling. Possible involvement of a vacuolar H(+)-ATPase E subunit. Miura, K., Miyazawa, S., Furuta, S., Mitsushita, J., Kamijo, K., Ishida, H., Miki, T., Suzukawa, K., Resau, J., Copeland, T.D., Kamata, T. J. Biol. Chem. (2001) [Pubmed]
  20. Leucine zipper-mediated homodimerization of the p21-activated kinase-interacting factor, beta Pix. Implication for a role in cytoskeletal reorganization. Kim, S., Lee, S.H., Park, D. J. Biol. Chem. (2001) [Pubmed]
  21. Regulation of the Dbl proto-oncogene by heat shock cognate protein 70 (Hsc70). Kauppinen, K.P., Duan, F., Wels, J.I., Manor, D. J. Biol. Chem. (2005) [Pubmed]
  22. N terminus of Sos1 Ras exchange factor: critical roles for the Dbl and pleckstrin homology domains. Qian, X., Vass, W.C., Papageorge, A.G., Anborgh, P.H., Lowy, D.R. Mol. Cell. Biol. (1998) [Pubmed]
  23. Growth arrest-inducing genes are activated in Dbl-transformed mouse fibroblasts. Melani, R., Sallustio, F., Fardin, P., Vanni, C., Ognibene, M., Ottaviano, C., Melillo, G., Varesio, L., Eva, A. Gene Expr. (2006) [Pubmed]
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