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

• Thus, the map location and linkage relationships of the Mcf-2 gene are similar in man and mouse, and this unique protooncogenic locus is part of a conserved linkage group on the mammalian X chromosome [10].
• In situ hybridization of the mouse Mcf-2 probe onto mouse metaphase chromosomes indicates that this gene lies in the same region of the X chromosome as Cf-9, the mouse gene for coagulation factor IX [10].
• Restriction and complexity of Mcf2 proto-oncogene expression [11].
• To assess its role in neurogenesis and gametogenesis, targeted deletion of the murine Dbl gene was accomplished in embryonic stem cells [12].
• Ezrin function is required for ROCK-mediated fibroblast transformation by the Net and Dbl oncogenes [13].

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].

References